Alpha-amylase variants and polynucleotides encoding same

ABSTRACT

The present invention relates to alpha-amylase variants. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 16/847,773filed on Apr. 14, 2020 (now pending) which is a divisional of U.S.application Ser. No. 15/571,219 filed May 9, 2016, now U.S. Pat. No.10,647,946 which is a 35 U.S.C. 371 national application ofPCT/EP2016/060266 filed May 9, 2016, which claims priority or thebenefit under 35 U.S.C. 119 of Indian application no. 2335/CHE/2015filed May 8, 2015, the contents of which are fully incorporated hereinby reference.

REFERENCE TO A SEQUENCE LISTING

This application contains a Sequence Listing in computer readable form,which is incorporated herein by reference.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to alpha-amylase variants, polynucleotidesencoding the variants, methods of producing the variants, and methods ofusing the variants.

Description of the Related Art

Alpha-amylases have for many years been used in laundry where is itwell-known that alpha-amylases have a beneficial effect in removal ofstarch containing, or starch-based, stains.

WO95/26397 discloses alkaline Bacillus amylases having good washperformance measured at temperatures in the range of 30-60° C.

WO00/60060 and WO00/60058 discloses further bacterial alpha-amylaseshaving good wash performance.

In recent years there has been a desire to reduce the temperature of thelaundry in order to reduce the energy consumption. Lowering thetemperature in laundry often means that the performance of the detergentcomposition and the enzyme is reduced and a lower wash performance istherefore obtained at low temperature. It is therefore desired to findnew alpha-amylases having good wash performance at low temperature.Accordingly, it is an object of the present invention to providealpha-amylases which have good wash performance at low temperature, suchas at 15° C. Thus, the present invention provides such further improvedalpha-amylase variants with improved properties compared to its parent.

SUMMARY OF THE INVENTION

The present invention relates to an alpha-amylase variant of a parentpolypeptide having alpha-amylase activity, wherein the variant is afusion polypeptide which has an improved wash performance at lowtemperature, and wherein said variant has alpha-amylase activity.

The present invention also relates to polynucleotides encoding thevariants; nucleic acid constructs, vectors, and host cells comprisingthe polynucleotides; and methods of producing the variants.

The present invention also relates to methods of improving washperformance of a parent alpha-amylase.

Conventions for Designation of Variants

For purposes of the present invention, the mature polypeptide disclosedin SEQ ID NO: 7 is used to determine the corresponding amino acidresidue in another alpha-amylase. Alternatively, the mature polypeptidedisclosed in SEQ ID NO: 13 and 14 may be used to determine thecorresponding amino acid residue in another alpha-amylase. The aminoacid sequence of another alpha-amylase is aligned with the maturepolypeptide disclosed in SEQ ID NO: 7, and based on the alignment, theamino acid position number corresponding to any amino acid residue inthe mature polypeptide disclosed in any of SEQ ID NOs: 13 and 14 isdetermined using the Needleman-Wunsch algorithm (Needleman and Wunsch,1970, J. Mol. Biol. 48: 443-453) as implemented in the Needle program ofthe EMBOSS package (EMBOSS: The European Molecular Biology Open SoftwareSuite, Rice et al., 2000, Trends Genet. 16: 276-277), preferably version5.0.0 or later. The parameters used are gap open penalty of 10, gapextension penalty of 0.5, and the EBLOSUM62 (EMBOSS version of BLOSUM62)substitution matrix.

Identification of the corresponding amino acid residue in anotheralpha-amylase can be determined by an alignment of multiple polypeptidesequences using several computer programs including, but not limited to,MUSCLE (multiple sequence comparison by log-expectation; version 3.5 orlater; Edgar, 2004, Nucleic Acids Research 32: 1792-1797), MAFFT(version 6.857 or later; Katoh and Kura, 2002, Nucleic Acids Research30: 3059-3066; Katoh et al., 2005, Nucleic Acids Research 33: 511-518;Katoh and Toh, 2007, Bioinformatics 23: 372-374; Katoh et al., 2009,Methods in Molecular Biology 537:_39-64; Katoh and Toh, 2010,Bioinformatics 26: 1899-1900), and EMBOSS EMMA employing ClustalW (1.83or later; Thompson et al., 1994, Nucleic Acids Research 22: 4673-4680),using their respective default parameters.

When the other enzyme has diverged from the mature polypeptide of SEQ IDNO: 7 such that traditional sequence-based comparison fails to detecttheir relationship (Lindahl and Elofsson, 2000, J. Mol, Bial, 295:613-615), other pairwise sequence comparison algorithms can be used.Greater sensitivity in sequence-based searching can be attained usingsearch programs that utilize probabilistic representations ofpolypeptide families (profiles) to search databases: For example, thePSI-BLAST program generates profiles through an iterative databasesearch process and is capable of detecting remote homologs (Atschul etal., 1997, Nucleic Acids Res. 25: 3389-3402). Even greater sensitivitycan be achieved if the family or superfamily for the polypeptide has oneor more representatives in the protein structure databases. Programssuch as GenTHREADER (Jones, 1999, J. Mol. Biol. 287: 797-815; McGuffinand Jones, 2003, Bioinformatics 19: 874-881) utilize information from avariety of sources (PSI-BLAST, secondary structure prediction,structural alignment profiles, and solvation potentials) as input to aneural network that predicts the structural fold for a query sequence.Similarly, the method of Gough et al., 2000, J. Mol. Biol. 313: 903-919,can be used to align a sequence of unknown structure with thesuperfamily models present in the SCOP database. These alignments can inturn be used to generate homology models for the polypeptide, and suchmodels can be assessed for accuracy using a variety of tools developedfor that purpose.

For proteins of known structure, several tools and resources areavailable for retrieving and generating structural alignments. Forexample the SCOP superfamilies of proteins have been structurallyaligned, and those alignments are accessible and downloadable. Two ormore protein structures can be aligned using a variety of algorithmssuch as the distance alignment matrix (Holm and Sander, 1998. Proteins33: 88-96) or combinatorial extension (Shindyalov and Bourne, 1998,Protein Engineering 11: 739-747), and implementation of these algorithmscan additionally be utilized to query structure databases with astructure of interest in order to discover possible structural homologs(e.g., Holm and Park, 2000, Bioinformatics 16: 566-567).

In describing the variants of the present invention, the nomenclaturedescribed below is adapted for ease of reference. The accepted IUPACsingle letter or three letter amino acid abbreviation is employed.

Substitutions: For an amino acid substitution, the followingnomenclature is used: Original amino acid, position, substituted aminoacid. Accordingly, the substitution of threonine at position 226 withalanine is designated as “Thr226Ala” or “T226A”. Multiple mutations areseparated by addition marks (“+”), e.g., “Gly205Arg+Ser411Phe” or“G205R+S411F”, representing substitutions at positions 205 and 411 ofglycine (G) with arginine (R) and serine (S) with phenylalanine (F),respectively.

Deletions: For an amino acid deletion, the following nomenclature isused: Original amino acid, position, *. Accordingly, the deletion ofglycine at position 195 Is designated as “Gly195*” or “G195*”. Multipledeletions are separated by addition marks (“+”), e. “Gly195*+Ser411*” or“G195*+S411*” Multiple modifications: Variants comprising multiplemodifications are separated by addition marks (“+”),“Arg170Tyr+Gly195Glu” or “R170Y+G195E” representing a substitution ofarginine and glycine at positions 170 and 195 with tyrosine and glutamicacid, respectively. Different modifications: Where differentmodifications can be introduced at a position, the different alterationsare separated by a comma, e.g., “Arg170Tyr,Glu” represents asubstitution of arginine at position 170 with tyrosine or glutamic acid.Thus, “Tyr167Gly,Ala+Arg170Gly,Ala” designates the following variants:

-   “Tyr167Gly+Arg170Gly”, “Tyr167Gly+Arg170Ala” “Tyr167Ala+Arg170Gly”,    and “Tyr167Ala+Arg170Ala”.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a set of sequences. For ease, these arelisted below;

SEQ ID NO: 1 is the nucleotide sequence of an alpha-amylase (AA110)

SEQ ID NO: 2 is the nucleotide sequence of an alpha-amylase originatingfrom Alicyclobacillus sp.

SEQ ID NO: 3 is the nucleotide sequence of an alpha-amylase originatingfrom Bacillus amyloliquefaciens.

SEQ ID NO: 4 is the amino acid sequence of AAI10 including the signalpeptide.

SEQ ID NO: 5 is the amino acid sequence of Alicyclobacillus sp.including the signal peptide.

SEQ ID NO: 6 is the amino acid sequence of Bacillus amyloliquefaciensincluding the signal peptide.

SEQ ID NO: 7 is the amino acid sequence of the mature AAI10 SEQ ID NO: 8is the amino acid sequence of the mature Alicyclobacillus sp.

SEQ ID NO: 9 is the amino acid sequence of the mature Bacillusamyloliquefaciens

SEQ ID NO: 10 is the amino acid sequence corresponding the A and Bdomains of AAI10.

SEQ ID NO: 11 is the amino acid sequence corresponding to the C domainof Alicyclobacillus sp.

SEQ ID NO: 12 is the amino acid sequence responding to the C domain ofBacillus amyloliquefaciens

SEQ ID NO: 13 is the amino acid sequence of the fusion polypeptideconsisting of the A and B domain of AAI10 and the C domain ofAlicyclobacillus sp.

SEQ ID NO: 14 is the amino acid sequence of the fusion polypeptideconsisting of the A and the B domains of AAI10 and the C domain ofBacillus amyloliquefaciens

SEQ ID NO: 15 is the amino acid sequence of the mature AA110alpha-amylase comprising a double deletion at positions corresponding topositions 182 and 183 of SEQ ID NO: 7.

Variants of the Invention

In one aspect, the present invention relates to variants of a parentpolypeptide having alpha-amylase activity. Thus, in particular aspect,the present invention relates to variant of a parent polypeptide havingalpha-amylase activity, wherein said variant is a fusion polypeptidewhich has an improved wash performance at low temperature, and whereinsaid variant has alpha-amylase activity.

It has been shown that variants according to the present invention haveimproved performance, such as wash performance, at a low temperature, inparticular at 15° C., in liquid detergent compositions.

The term “variant” as used herein, refers to a polypeptide havingalpha-amylase activity comprising an alteration, i.e., a substitution,insertion, and/or deletion, at one or more (e.g., several) positions. Asubstitution means replacement of the amino acid occupying a positionwith a different amino acid; a deletion means removal of the amino acidoccupying a position; and an insertion means adding an amino acidadjacent to and immediately following the amino acid occupying aposition, all as defined above. The variants of the present inventionhave at least 20%, e.g., at least 40%, at least 50%, at least 60%, atleast 70%, at least 80%, at least 90%, at least 95%, or at least 100% ofthe alpha-amylase activity of the polypeptide of SEQ ID NOs: 7, 13, 14,15, or the mature polypeptide of SEQ ID NO: 4. The variants of thepresent invention have at least 65%, such as at least 70%, such as atleast 75%, such as at least 80%, such as at least 85%, such at least90%, such as at least 95%, such as at least 97%, such as at least 99%,but less than 100% sequence identity to any one of SEQ ID NOs; 4, 7, 13,14, or 15

The term “parent polypeptide” as used herein, refers to a polypeptide towhich an alteration is made to produce enzyme variants. The polypeptidehaving any of SEQ ID NOs: 4, 7, 13, 14, and 15 may e.g. be a parent forthe variants of the present invention. Any polypeptide having at least65%, such as at least 70%, such as at least 75%, such as at least 80%,such as at least 85%, such at least 90%, such as at least 95%, such asat least 97%, such as at least 99%, sequence identity to any one of SEQID NOs: 4, 7, 13, 14, or 15 may also be a parent polypeptide for thevariants of the present invention.

The parent polypeptide may be a fusion polypeptide or cleavable fusionpolypeptide. Such fusion polypeptide may consist of a subsequence of oneparent polypeptide and a subsequence of second parent polypeptide. Inparticular, a fusion polypeptide may consist of an A and B domain of onespecies of alpha-amylase and a C domain of another species ofalpha-amylase, and thereby providing a parent polypeptide to generate avariant of the present invention. Techniques for producing fusionpolypeptides are known in the art, and include ligating the codingsequences encoding the polypeptides so that they are in frame and thatexpression of the fusion polypeptide is under control of the samepromoter(s) and terminator. Fusion polypeptides may also be constructedusing intein technology in which fusion polypeptides are createdpost-translationally (Cooper et al., 1993, EMBO J. 12: 2575-2583; Dawsonet al., 1994, Science 266: 776-779).

A fusion polypeptide may further comprise a cleavage site between thetwo polypeptides. Upon secretion of the fusion protein, the site iscleaved releasing the two polypeptides. Examples of cleavage sitesinclude, but are not limited to, the sites disclosed in Martin et al.,2003, J. Ind. Microbiol. Biotechnol. 3: 568-576; Svetina et al., 2000,J. Biotechnol, 76: 245-251; Rasmussen-Wilson et al., 1997, App. Environ,Microbiol. 63: 3488-3493; Ward et al., 1995, Biotechnology 13: 498-503;and Contreras et al., 1991, Biotechnology 9; 378-381; Eaton et al.,1986. Biochemistry 25: 505-512; Collins-Racie et a, 1995, Biotechnology13: 982-987; Carter et al., 1989, Proteins: Structure, Function, andGenetics 6: 240-248; and Stevens, 2003, Drug Discovery World 4: 35-48.

The parent polypeptide may be obtained from microorganisms of any genus.For purposes of the present invention, the term “obtained from” as usedherein in connection with a given source shall mean that the parentpolypeptide encoded by a polynucleotide is produced by the source or bya strain in which the polynucleotide from the source has been inserted.

In some aspects of the present invention, the parent polypeptide isBacillus sp. alpha-amylase, e.g., the alpha-amylase of SEQ ID NOs: 4,the mature polypeptide thereof, ie. SEQ ID NO: 7. In particular aspects,the parent polypeptide is a fusion protein, and originates from both aBacillus sp and a Alicyclobacilius sp., e.g. the alpha-amylase of SEQ IDNO: 13. In other aspects, the parent polypeptide is a fusion protein andoriginates from two different Bacillus sps., e.g, resulting in thealpha-amylase of SEQ ID NO: 14.

It will be understood that for the aforementioned species, the inventionencompasses both the perfect and imperfect states, and other taxonomicequivalents, e.g., anamorphs, regardless of the species name by whichthey are known. Those skilled in the art will readily recognize theidentity of appropriate equivalents.

Strains of these species are readily accessible to the public in anumber of culture collections, such as the American Type CultureCollection (ATCC), Deutsche Sammlung von Mikroorganismen andZellkulturen GmbH (DSMZ), Centraalbureau Voor Schimmelcultures (CBS),and Agricultural Research Service Patent Culture Collection, NorthernRegional Research Center (NRRL).

The parent polypeptide may be identified and obtained from other sourcesincluding microorganisms isolated from nature (e.g., soil, composts,water, etc.) or DNA samples obtained directly from natural materials(e.g., soil, composts, water, etc.) using the above-mentioned probes.Techniques for isolating microorganisms and DNA directly from naturalhabitats are well known in the art. A polynucleotide encoding a parentpolypeptide may then be obtained by similarly screening a genomic DNA orcDNA library of another microorganism or mixed DNA sample. Once apolynucleotide encoding a parent polypeptide has been detected with theprobe(s), the polynucleotide can be isolated or cloned by utilizingtechniques that are known to those of ordinary skill in the art (see,e.g., Sambrook et al., 1989, supra).

In one embodiment, the parent polypeptide comprises or consists of theamino acid sequence set forth in SEQ ID NO: 7, 13, or 15. In anotherembodiment, the parent polypeptide comprises or consists of the maturepolypeptide of SEQ ID NO: 4. In particular, the parent polypeptide maycomprise or consist of amino acids 1 to 485 of SEQ ID NO: 4.

In another embodiment, the parent polypeptide is a fragment of themature polypeptide of SEQ ID NO: 4 containing at least 350, such as atleast 390 amino acid residues, e.g., at least 395 and at least 397 aminoacid residues of SEQ ID NO: 4.

In another embodiment, the parent polypeptide is an allelic variant ofthe mature polypeptide of SEQ ID NO: 4.

The term “sequence identity” as used herein, refers to the relatednessbetween two amino acid sequences or between two nucleotide sequences.For purposes of the present invention, the sequence identity between twoamino acid sequences is determined using the Needleman-Wunsch algorithm(Needleman and Wunsch, 1970, J. Mol. Biol. 48: 443-453) as implementedin the Needle program of the EMBOSS package (EMBOSS: The EuropeanMolecular Biology Open Software Suite, Rice et al., 2000, Trends Genet.16: 276-277), preferably version 5.0.0 or later. The parameters used aregap open penalty of 10, gap extension penalty of 0.5, and the EBLOSUM62(EMBOSS version of BLOSUM62) substitution matrix. The output of Needlelabeled “longest identity” (obtained using the—nobrief option) is usedas the percent identity and is calculated as follows:

(Identical Residues×100)/(Length of Alignment Total Number of Gaps inAlignment)

For purposes of the present invention, the sequence identity between twodeoxyribonucleotide sequences is determined using the Needleman-Wunschalgorithm (Needleman and Wunsch, 1970, supra) as implemented in theNeedle program of the EMBOSS package (EMBOSS: The European MolecularBiology Open Software Suite, Rice et al., 2000, supra), preferablyversion 5.0.0 or later. The parameters used are gap open penalty of 10,gap extension penalty of 0.5, and the EDNAFULL (EMBOSS version of NCBINUC4.4) substitution matrix. The output of Needle labeled “longestidentity” (obtained using the nobrief option) is used as the percentidentity and is calculated as follows:

(Identical Deoxyribonucleotides×100)/(Length of Alignment Total Numberof Gaps in Alignment)

The term “alpha-amylase activity” as used herein, refers to the activityof alpha-1,4-glucan-4-glucanohydrolases, E.C. 3.2.1.1, which constitutea group of enzymes, catalyzing hydrolysis of starch and other linear andbranched 1,4-glucosidic oligo- and polysaccharides. Thus, the term“alpha-amylase” as used herein, refers to an enzyme that hasalpha-amylase activity (Enzyme Class; EC 3.2.1.1) that hydrolyses alphabonds of large, alpha-linked polysaccharides, such as starch andglycogen, yielding glucose and maltose. The terms “alpha-amylase” and“amylase” may be used interchangeably and constitute the same meaningand purpose within the scope of the present invention. For purposes ofthe present invention, alpha-amylase activity is determined according tothe procedure described in the Examples. In one embodiment, the variantsof the present invention have at least 20%, e.g.; at least 40%, at least50%, at least 60%, at least 70%, at least 80%, at least 90%, at least95%, or at least 100% of the alpha-amylase activity of the polypeptideof SEQ ID NOs: 7, 13, 14, or 15; or the mature polypeptide of SEQ ID NO:4.

The term “fusion polypeptide” as used herein, refers to a polypeptidewhich comprises amino acid sequences originating from more than one,such as two, three, or four, species. Such a fusion polypeptide may havebeen generated by molecular techniques well-Known to the skilled person.A fusion polypeptide of the present invention has alpha-amylaseactivity. In particular, a fusion polypeptide of the present invention,comprises e.g. an A and B domain of one alpha-amylase and a C domainfrom another alpha-amylase.

The term “wash performance” as used herein, refers to an enzyme'sability to remove starch or starch-containing stains present on theobject to be cleaned during e.g. laundry or hard surface cleaning, suchas dish wash. The term “wash performance” includes cleaning in generale.g, hard surface cleaning as in dish wash, but also wash performance ontextiles such as laundry, and also industrial and institutionalcleaning. The wash performance may be quantified by calculating theso-called Intensity value, and results may be displayed as “ImprovementFactor” (IF). Wash performance may be determined as in described in theExamples herein.

The term “Intensity value” as used herein, refers to the washperformance measured as the brightness expressed as the intensity of thelight reflected from the sample when illuminated with white light. Whenthe sample is stained the intensity of the reflected light is lower,than that of a clean sample. Therefore the intensity of the reflectedlight can be used to measure wash performance, where a higher intensityvalue correlates with higher wash performance.

Color measurements are made with a professional flatbed scanner (KodakiQsmart, Kodak) used to capture an image of the washed textile.

To extract a value for the light intensity from the scanned images,24-bit pixel values from the image are converted into values for red,green and blue (RGB). The intensity value (Int) is calculated by addingthe RGB values together as vectors and then taking the length of theresulting vector:

${Int} = \sqrt{r^{2} + g^{2} + b^{2}}$

The term “improved wash performance” as used herein, refers to animprovement of the wash performance of an alpha-amylase of the presentinvention relative to the wash performance of the parent polypeptide.Improved wash performance may be measured by comparing of the so-calledIntensity value and calculating the Improvement Factor (IF). Theimproved wash performance is determined according to the section “Washperformance of alpha-amylases using Automatic Mechanical Stress Assay”and using model detergent J at 15° C., 30° C. or 40° C. Other modeldetergents may be used, such as Model detergent A.

Thus, in one embodiment, the improved wash performance is determined bya method comprising the steps of;

-   -   a) washing a fabric stained with starch with an alpha-amylase        variant and a parent polypeptide sample added, respectively, to        a model detergent composition, such as Model A or Model J;    -   b) measuring the intensity of light reflected from the sample        when illuminated with white light; and    -   c) optionally, calculating the improvement factor (IF) as the        ratio of delta intensity of the alpha-amylase sample over the        delta intensity of the parent polypeptide sample.

In one embodiment, the improved wash performance is determined by amethod comprising the steps of;

-   -   a) washing a fabric stained with starch with an alpha-amylase        variant and a parent polypeptide sample added, respectively, to        a model detergent composition, such as Model A or Model J for 20        minutes at 15° C., 30° C., and 40° C.;    -   b) measuring the intensity of light reflected from the sample        when illuminated with white light; and    -   c) optionally, calculating the improvement factor (IF) as the        ration of delta intensity of the alpha-amylase sample over the        delta intensity of the parent polypeptide sample.

The term “low temperature” as used herein, refers to is a temperature of5-40° C., such as 5-35° C., preferably 5-30° C., more preferably 5-25°C., more preferably 5-20° C., most preferably 5-15° C., and inparticular 5-10° C., In a preferred embodiment, “Low temperature” is atemperature of 10-35° C., preferably 10-30° C. more preferably 10-25°C., most preferably 10-20° C., and in particular 10-15° C. Mostpreferred, low temperature means 15° C.

Thus, in one embodiment, the low temperature is 5° C. to 40° C.,preferably 10° C. to 30°, event more preferred 15° C. to 20° C.

In one embodiment, the improved wash performance has an ImprovementFactor (IF) of ≥1 when compared to said parent polypeptide havingalpha-amylase activity.

The term “Improvement Factor” as used herein, refers to a quantitativeway of calculating the improvement of a particular property of a variantaccording to the present invention. Determination of the ImprovementFactor may be according to the following formula:

$\frac{{{Intensity}\mspace{14mu}{value}\mspace{14mu}{of}\mspace{14mu}{variant}} - {{Intensity}\mspace{14mu}{value}\mspace{14mu}{of}\mspace{14mu}{blank}}}{{{Intensity}\mspace{14mu}{value}\mspace{14mu}{of}\mspace{14mu}{parent}} - {{Intensity}\mspace{14mu}{value}\mspace{14mu}{of}\mspace{14mu}{blank}}}$

Other formulas may be used to determine the Improvement Factor. Theskilled person knows the presently presented formula as well asalternative ways of calculating the Improvement Factor.

According to the present invention, a value of 1.0 corresponds to theperformance observed for the parent polypeptide. A value above 1.0indicates an improvement of performance of the variant tested comparedto the parent polypeptide. Accordingly, any value of ≥1.0 is indicativefor improvement of property, such as performance, of the variantcompared to the parent polypeptide.

According to the present invention, a variant showing improvement ofproperty under at least one condition tested, is considered a varianthaving improved property as compared to the parent polypeptide.

In one embodiment, said parent polypeptide comprises an A and a B domaincomprising the amino acid sequence of SEQ ID NO: 10, or an A and a Bdomain having at least 80%, such as 85%, such as 90%, such as 95%, suchas 97% sequence identity to SEQ ID NO: 10, and a C domain of a lowtemperature alpha-amylase.

The terms “A domain”, “B domain” and “C domain” as used herein, refersto three distinct domains A, B and C, all part of the alpha-amylasestructure, see, e.g., Machius et al., 1995, J. Mol. Biol. 246: 545-559,Thus, an alpha-amylase, such as a parent polypeptide and a variantaccording to the invention, may comprise both an A, 8, and C domain. Theterm “domain” means a region of a polypeptide that in itself forms adistinct and independent substructure of the whole molecule.Alpha-amylases consist of a beta/alpha-8 barrel harboring the activesite residues, which is denoted the A domain, a rather long loop betweenthe beta-sheet 3 and alpha-helix 3, which is denoted the B domain(together; “A and B domain”), and a C-domain and in some cases also acarbohydrate binding domain (e.g., WO 2005/001064; Machius et al.,supra).

The domains of an alpha-amylase may be determined by structure analysissuch as using crystallographically techniques. An alternative method fordetermining the domains of an alpha-amylase is by sequence alignment ofthe amino acid sequence of the alpha-amylase with another alpha-amylasefor which the domains have been determined. The sequence that alignswith, e.g., the C-domain sequence in the alpha-amylase for which theC-domain has been determined can be considered the C domain for thegiven alpha-amylase.

The term “A and B domain” as used herein, refers to two domains of analpha-amylase taken as one unit, whereas the C domain is another unit ofthe alpha-amylases. Thus, the amimo acid sequence of the “A and Bdomain” is understood as one sequence or one part of a sequence of analpha-amylase comprising an “A and B domain” and other domains (such asthe C domain). Thus, the term “the A and B domain domain has at least65% sequence identity to SEQ ID NO: 10” means that the amino acidsequence that form the A and B domain has at least 65% sequence identityto SEQ ID NO: 10. As used herein, the “A and B domain” of a parentpolypeptide corresponds to amino acids 1 to 399 of SEQ ID NO: 7, or toamino acids 1 to 397 of SEQ ID NO: 15. The A and B domain of a parentpolypeptide may have the amino acid sequence of SEQ ID NO: 10.

The term “C domain” as used herein, refers to a domain of analpha-amylase as one unit. The “C domain” of an alpha-amylasecorresponds to amino acids 400 to 485 of SEQ ID NO: 7, or to amino acid398 to 483 of SEQ ID NO: 15, Thus, the C domain of an alpha amylase maybe found by alignment of said alpha-amylase with the polypeptide of SEQID NO: 7 or 15. The part of said alpha-amylase that aligns with aminoacids 400 to 485 of SEQ ID NO: 7 or to amino acids 398 to 483 of SEQ IDNO: 15 is according to the present invention “the C domain” of thealpha-amylase. The C domain of a parent polypeptide may have the aminoacid sequence of SEQ ID NOs: 11 or 12.

The term “C domain of a low temperature alpha-amylase” as used herein,refers to the C domain of an alpha-amylase showing particular propertiesat low temperatures. Non-limiting examples of such low temperaturealpha-amylases are those originating from Alicyclobacillus sp. as wellas from Bacillus amyloliquefaciens (BAN).

In one embodiment, the parent polypeptide comprises a C domaincomprising the amino acid sequence of SEQ ID NOs: 11 or 12, or a Cdomain having at 80%, such as 85%, such as 90%, such as 95%, such as97%, sequence identity to SEQ ID NO: 11 or 12.

In one embodiment, the parent polypeptide comprises the amino acidsequence of SEQ ID NOs: 13 or 14, or a sequence having at least 80%,such as 85%, such as 90%, such as 95%, such as 97% sequence identity toSEQ ID NOs: 13 or 14.

As stated elsewhere herein, the parent polypeptide may be anypolypeptide having alpha-amylase activity and at least 65% sequenceidentity to any one of the amino acid sequences as set forth in SEQ IDNOs: 13 and 14. In certain embodiments, the parent polypeptide comprisesthe amino acid sequences as set forth in SEQ ID NOs: 10, 11, and 12.

In one embodiment, the parent polypeptide a sequence identity to theamino acid sequence set forth in SEQ ID NOs: 13 or 14 of at least 60%,e.g., at least 65%, at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 91%, at least 92%, at least 93%, at least94%, at least 95%, at least 96%, at least 97%, at least 98%, at least99%, or 100%, and which parent polypeptide has alpha-amylase activity.In one embodiment, the amino acid sequence of the parent polypeptidediffers by up to 10 amino acids, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10,from the amino acid sequences set forth in SEQ ID NOs: 7, 13, and 14.

The present invention provides variants of such parent polypeptides.

The variants according to the present invention may advantageouslycomprise alterations in specific positions of the A and B domain. Thus,in a particular embodiment, the variant comprises amino acid alterationsin amino acid positions corresponding the amino acid sequence set forthin SEQ ID NO: 10, or a sequence having at least 65% sequence identity tothe amino acid sequence set forth in SEQ ID NO: 10.

In particular, the present invention relates to an embodiment, the A andB domains comprise a modification in one or more of the followingpositions corresponding to positions; H1, T5, G7, Q11, N16, V17, Q32,A37, 140, P45, W48, G50, T51, N54, V56, A60, K72, R87, Q98, M105, G109,F113, R116, Q118, Q125, G133, T134, W140, G142, G149, I165, W167, Q169,R171, Q172, L173, A174, G184, A186, E190, I193, N195, G196, A204, V206,P211, I214, V215, L217, L219, A225, L228, L235, V238, K242, S244, M246,M248, L250, G255, Q256, N260, A263, V264, A265, Y267, K269, N270, G273,S280, W284, T285, M286, F289, V291, N295, Q299, S304, R320, H321, S323,H324, V326, F328, T334, D337, Q345, G346, G348, T355, S376, D377, D379,Y382, S383, Q385, K391, K393, and Q395 of SEQ ID NOs: 7 or 10.

Such variants have shown to have improved wash performance in at leastone assay wherein the temperature under which the variants have beentested was a low temperature, such as 15° C., 30° and 40° C. Specificconditions may be seen in the Examples herein.

The term “modification” as used herein, refers to both substitutions anddeletions of amino acid within the amino acid sequence of a polypeptide.The terms “alteration” and “modification” may be used interchangeablyherein. This should not be understood as any limitation and thus, theterms constitute the same meaning and purpose unless explicitly statedotherwise.

The term “corresponding to” as used herein, refers to way of determiningthe specific amino acid of a sequence wherein reference is made to aspecific amino acid sequence. E.g. for the purposes of the presentinvention, when references are made to specific amino acid positions,the skilled person would be able to align another amino acid sequence tosaid amino acid sequence that reference has been made to, in order todetermine which specific amino acid may be of interest in said anotheramino acid sequence. Alignment of another amino acid sequence with e.g.the sequence as set forth in SEQ ID NO: 4, 7, or any other sequencelisted herein, has been described elsewhere herein. Alternativealignment methods may be used, and are well-known for the skilledperson.

In a particular embodiment, the variant comprises an alteration in two,three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, or sixteen positions corresponding to thefollowing positions; H1, T5, G7, Q11, N16, V17, Q32, A37, T40, P45, W48,G50, T51, N54, V56, A60, K72, R87, Q98, M105, G109, F113, R116, Q118,Q125, G133, T134, W140, G142, G149, T165, W167, Q169, R171, Q172, L173,A174, G184, A186, E190, T193, N195, G196, A204, V206, P211, I214, V215,L217, L219, A225, L228, L235, V238, K242, S244, M246, M248, L250, G255,Q256, N260, A263, V264, A265, Y267, K269, N270, G273, S280, W284, T285,M286, F289, V291, Y295, Q299, S304, R320, H321, S323, H324, V326, F328,T334, D337, Q345, G346, G348, T355, S376, D377, D379, Y382, S383, Q385,K391, K393, and Q395 of SEQ ID NOs: 7 or 10.

In a particular embodiment, the variant comprises an alteration in thefollowing positions;

H1 + T5 T40 + L217 N54 + T285 Q125 + G255 G184 + P211 M248 + Q299 H1 +G7 T40 + L219 N54 + M286 Q125 + Q256 G184 + I214 M248 + S304 H1 + Q11T40 + L228 N54 + F289 Q125 + A263 G184 + V215 M248 + R320 H1 + N16 T40 +L235 N54 + V291 Q125 + V264 G184 + L217 M248 + H321 H1 + V17 T40 + V238N54 + Q299 Q125 + A265 G184 + L219 M248 + S323 H1 + Q32 T40 + M246 N54 +S304 Q125 + Y267 G184 + L228 M248 + H324 H1 + A37 T40 + M248 N54 + R320Q125 + N270 G184 + L235 M248 + F328 H1 + T40 T40 + L250 N54 + H321Q125 + G273 G184 + V238 M248 + T334 H1 + P45 T40 + G255 N54 + S323Q125 + S280 G184 + M246 M248 + D337 H1 + W48 T40 + Q256 N54 + H324Q125 + T285 G184 + M248 M248 + Q345 H1 + G50 T40 + A263 N54 + F328Q125 + M286 G184 + L250 M248 + G346 H1 + T51 T40 + V264 N54 + T334Q125 + F289 G184 + G255 M248 + G348 H1 + N54 T40 + A265 N54 + D337Q125 + V291 G184 + Q256 M248 + T355 H1 + V56 T40 + Y267 N54 + Q345Q125 + Q299 G184 + A263 M248 + S376 H1 + A60 T40 + N270 N54 + G346Q125 + S304 G184 + V264 M248 + D377 H1 + K72 T40 + G273 N54 + G348Q125 + R320 G184 + A265 M248 + D379 H1 + R87 T40 + S280 N54 + T355Q125 + H321 G184 + Y267 M248 + Y382 H1 + Q98 T40 + T285 N54 + S376Q125 + S323 G184 + N270 M248 + S383 H1 + M105 T40 + M286 N54 + D377Q125 + H324 G184 + G273 M248 + Q385 H1 + G109 T40 + F289 N54 + D379Q125 + F328 G184 + S280 M248 + K391 H1 + F113 T40 + V291 N54 + Y382Q125 + T334 G184 + T285 M248 + K393 H1 + R116 T40 + Q299 N54 + S383Q125 + D337 G184 + M286 M248 + Q395 H1 + Q118 T40 + S304 N54 + Q385Q125 + Q345 G184 + F289 L250 + G255 H1 + Q125 T40 + R320 N54 + K391Q125 + G346 G184 + V291 L250 + Q256 H1 + G133 T40 + H321 N54 + K393Q125 + G348 G184 + Q299 L250 + A263 H1 + T134 T40 + S323 N54 + Q395Q125 + T355 G184 + S304 L250 + V264 H1 + W140 T40 + H324 V56 + A60Q125 + S376 G184 + R320 L250 + A265 H1 + G142 T40 + F328 V56 + K72Q125 + D377 G184 + H321 L250 + Y267 H1 + G149 T40 + T334 V56 + R87Q125 + D379 G184 + S323 L250 + N270 H1 + T165 T40 + D337 V56 + Q98Q125 + Y382 G184 + H324 L250 + G273 H1 + W167 T40 + Q345 V56 + M105Q125 + S383 G184 + F328 L250 + S280 H1 + R171 T40 + G346 V56 + G109Q125 + Q385 G184 + T334 L250 + T285 H1 + Q172 T40 + G348 V56 + F113Q125 + K391 G184 + D337 L250 + M286 H1 + L173 T40 + T355 V56 + R116Q125 + K393 G184 + Q345 L250 + F289 H1 + A174 T40 + S376 V56 + Q118Q125 + Q395 G184 + G346 L250 + V291 H1 + G184 T40 + D377 V56 + Q125G133 + T134 G184 + G348 L250 + Q299 H1 + T193 T40 + D379 V56 + G133G133 + W140 G184 + T355 L250 + S304 H1 + N195 T40 + Y382 V56 + T134G133 + G142 G184 + S376 L250 + R320 H1 + G196 T40 + S383 V56 + W140G133 + G149 G184 + D377 L250 + H321 H1 + A204 T40 + Q385 V56 + G142G133 + T165 G184 + D379 L250 + S323 H1 + V206 T40 + K391 V56 + G149G133 + W167 G184 + Y382 L250 + H324 H1 + P211 T40 + K393 V56 + T165G133 + R171 G184 + S383 L250 + F328 H1 + I214 T40 + Q395 V56 + W167G133 + Q172 G184 + Q385 L250 + T334 H1 + V215 P45 + W48 V56 + R171G133 + L173 G184 + K391 L250 + D337 H1 + L217 P45 + G50 V56 + Q172G133 + A174 G184 + K393 L250 + Q345 H1 + L219 P45 + T51 V56 + L173G133 + G184 G184 + Q395 L250 + G346 H1 + L228 P45 + N54 V56 + A174G133 + T193 T193 + N195 L250 + G348 H1 + L235 P45 + V56 V56 + G184G133 + N195 T193 + G196 L250 + T355 H1 + V238 P45 + A60 V56 + T193G133 + G196 T193 + A204 L250 + S376 H1 + M246 P45 + K72 V56 + N195G133 + A204 T193 + V206 L250 + D377 H1 + M248 P45 + R87 V56 + G196G133 + V206 T193 + P211 L250 + D379 H1 + L250 P45 + Q98 V56 + A204G133 + P211 T193 + I214 L250 + Y382 H1 + G255 P45 + M105 V56 + V206G133 + I214 T193 + V215 L250 + S383 H1 + Q256 P45 + G109 V56 + P211G133 + V215 T193 + L217 L250 + Q385 H1 + A263 P45 + F113 V56 + I214G133 + L217 T193 + L219 L250 + K391 H1 + V264 P45 + R116 V56 + V215G133 + L219 T193 + L228 L250 + K393 H1 + A265 P45 + Q118 V56 + L217G133 + L228 T193 + L235 L250 + Q395 H1 + Y267 P45 + Q125 V56 + L219G133 + L235 T193 + V238 G255 + Q256 H1 + N270 P45 + G133 V56 + L228G133 + V238 T193 + M246 G255 + A263 H1 + G273 P45 + T134 V56 + L235G133 + M246 T193 + M248 G255 + V264 H1 + S280 P45 + W140 V56 + V238G133 + M248 T193 + L250 G255 + A265 H1 + T285 P45 + G142 V56 + M246G133 + L250 T193 + G255 G255 + Y267 H1 + M286 P45 + G149 V56 + M248G133 + G255 T193 + Q256 G255 + N270 H1 + F289 P45 + T165 V56 + L250G133 + Q256 T193 + A263 G255 + G273 H1 + V291 P45 + W167 V56 + G255G133 + A263 T193 + V264 G255 + S280 H1 + Q299 P45 + R171 V56 + Q256G133 + V264 T193 + A265 G255 + T285 H1 + S304 P45 + Q172 V56 + A263G133 + A265 T193 + Y267 G255 + M286 H1 + R320 P45 + L173 V56 + V264G133 + Y267 T193 + N270 G255 + F289 H1 + H321 P45 + A174 V56 + A265G133 + N270 T193 + G273 G255 + V291 H1 + S323 P45 + G184 V56 + Y267G133 + G273 T193 + S280 G255 + Q299 H1 + H324 P45 + T193 V56 + N270G133 + S280 T193 + T285 G255 + S304 H1 + F328 P45 + N195 V56 + G273G133 + T285 T193 + M286 G255 + R320 H1 + T334 P45 + G196 V56 + S280G133 + M286 T193 + F289 G255 + H321 H1 + D337 P45 + A204 V56 + T285G133 + F289 T193 + V291 G255 + S323 H1 + Q345 P45 + V206 V56 + M286G133 + V291 T193 + Q299 G255 + H324 H1 + G346 P45 + P211 V56 + F289G133 + Q299 T193 + S304 G255 + F328 H1 + G348 P45 + I214 V56 + V291G133 + S304 T193 + R320 G255 + T334 H1 + T355 P45 + V215 V56 + Q299G133 + R320 T193 + H321 G255 + D337 H1 + S376 P45 + L217 V56 + S304G133 + H321 T193 + S323 G255 + Q345 H1 + D377 P45 + L219 V56 + R320G133 + S323 T193 + H324 G255 + G346 H1 + D379 P45 + L228 V56 + H321G133 + H324 T193 + F328 G255 + G348 H1 + Y382 P45 + L235 V56 + S323G133 + F328 T193 + T334 G255 + T355 H1 + S383 P45 + V238 V56 + H324G133 + T334 T193 + D337 G255 + S376 H1 + Q385 P45 + M246 V56 + F328G133 + D337 T193 + Q345 G255 + D377 H1 + K391 P45 + M248 V56 + T334G133 + Q345 T193 + G346 G255 + D379 H1 + K393 P45 + L250 V56 + D337G133 + G346 T193 + G348 G255 + Y382 H1 + Q395 P45 + G255 V56 + Q345G133 + G348 T193 + T355 G255 + S383 T5 + G7 P45 + Q256 V56 + G346 G133 +T355 T193 + S376 G255 + Q385 T5 + Q11 P45 + A263 V56 + G348 G133 + S376T193 + D377 G255 + K391 T5 + N16 P45 + V264 V56 + T355 G133 + D377T193 + D379 G255 + K393 T5 + V17 P45 + A265 V56 + S376 G133 + D379T193 + Y382 G255 + Q395 T5 + Q32 P45 + Y267 V56 + D377 G133 + Y382T193 + S383 Q256 + A263 T5 + A37 P45 + N270 V56 + D379 G133 + S383T193 + Q385 Q256 + V264 T5 + T40 P45 + G273 V56 + Y382 G133 + Q385T193 + K391 Q256 + A265 T5 + P45 P45 + S280 V56 + S383 G133 + K391T193 + K393 Q256 + Y267 T5 + W48 P45 + T285 V56 + Q385 G133 + K393T193 + Q395 Q256 + N270 T5 + G50 P45 + M286 V56 + K391 G133 + Q395N195 + G196 Q256 + G273 T5 + T51 P45 + F289 V56 + K393 T134 + W140N195 + A204 Q256 + S280 T5 + N54 P45 + V291 V56 + Q395 T134 + G142N195 + V206 Q256 + T285 T5 + V56 P45 + Q299 A60 + K72 T134 + G149 N195 +P211 Q256 + M286 T5 + A60 P45 + S304 A60 + R87 T134 + T165 N195 + I214Q256 + F289 T5 + K72 P45 + R320 A60 + Q98 T134 + W167 N195 + V215 Q256 +V291 T5 + R87 P45 + H321 A60 + M105 T134 + R171 N195 + L217 Q256 + Q299T5 + Q98 P45 + S323 A60 + G109 T134 + Q172 N195 + L219 Q256 + S304 T5 +M105 P45 + H324 A60 + F113 T134 + L173 N195 + L228 Q256 + R320 T5 + G109P45 + F328 A60 + R116 T134 + A174 N195 + L235 Q256 + H321 T5 + F113P45 + T334 A60 + Q118 T134 + G184 N195 + V238 Q256 + S323 T5 + R116P45 + D337 A60 + Q125 T134 + T193 N195 + M246 Q256 + H324 T5 + Q118P45 + Q345 A60 + G133 T134 + N195 N195 + M248 Q256 + F328 T5 + Q125P45 + G346 A60 + T134 T134 + G196 N195 + L250 Q256 + T334 T5 + G133P45 + G348 A60 + W140 T134 + A204 N195 + G255 Q256 + D337 T5 + T134P45 + T355 A60 + G142 T134 + V206 N195 + Q256 Q256 + Q345 T5 + W140P45 + S376 A60 + G149 T134 + P211 N195 + A263 Q256 + G346 T5 + G142P45 + D377 A60 + T165 T134 + I214 N195 + V264 Q256 + G348 T5 + G149P45 + D379 A60 + W167 T134 + V215 N195 + A265 Q256 + T355 T5 + T165P45 + Y382 A60 + R171 T134 + L217 N195 + Y267 Q256 + S376 T5 + W167P45 + S383 A60 + Q172 T134 + L219 N195 + N270 Q256 + D377 T5 + R171P45 + Q385 A60 + L173 T134 + L228 N195 + G273 Q256 + D379 T5 + Q172P45 + K391 A60 + A174 T134 + L235 N195 + S280 Q256 + Y382 T5 + L173P45 + K393 A60 + G184 T134 + V238 N195 + T285 Q256 + S383 T5 + A174P45 + Q395 A60 + T193 T134 + M246 N195 + M286 Q256 + Q385 T5 + G184W48 + G50 A60 + N195 T134 + M248 N195 + F289 Q256 + K391 T5 + T193 W48 +T51 A60 + G196 T134 + L250 N195 + V291 Q256 + K393 T5 + N195 W48 + N54A60 + A204 T134 + G255 N195 + Q299 Q256 + Q395 T5 + G196 W48 + V56 A60 +V206 T134 + Q256 N195 + S304 A263 + V264 T5 + A204 W48 + A60 A60 + P211T134 + A263 N195 + R320 A263 + A265 T5 + V206 W48 + K72 A60 + I214T134 + V264 N195 + H321 A263 + Y267 T5 + P211 W48 + R87 A60 + V215T134 + A265 N195 + S323 A263 + N270 T5 + I214 W48 + Q98 A60 + L217T134 + Y267 N195 + H324 A263 + G273 T5 + V215 W48 + M105 A60 + L219T134 + N270 N195 + F328 A263 + S280 T5 + L217 W48 + G109 A60 + L228T134 + G273 N195 + T334 A263 + T285 T5 + L219 W48 + F113 A60 + L235T134 + S280 N195 + D337 A263 + M286 T5 + L228 W48 + R116 A60 + V238T134 + T285 N195 + Q345 A263 + F289 T5 + L235 W48 + Q118 A60 + M246T134 + M286 N195 + G346 A263 + V291 T5 + V238 W48 + Q125 A60 + M248T134 + F289 N195 + G348 A263 + Q299 T5 + M246 W48 + G133 A60 + L250T134 + V291 N195 + T355 A263 + S304 T5 + M248 W48 + T134 A60 + G255T134 + Q299 N195 + S376 A263 + R320 T5 + L250 W48 + W140 A60 + Q256T134 + S304 N195 + D377 A263 + H321 T5 + G255 W48 + G142 A60 + A263T134 + R320 N195 + D379 A263 + S323 T5 + Q256 W48 + G149 A60 + V264T134 + H321 N195 + Y382 A263 + H324 T5 + A263 W48 + T165 A60 + A265T134 + S323 N195 + S383 A263 + F328 T5 + V264 W48 + W167 A60 + Y267T134 + H324 N195 + Q385 A263 + T334 T5 + A265 W48 + R171 A60 + N270T134 + F328 N195 + K391 A263 + D337 T5 + Y267 W48 + Q172 A60 + G273T134 + T334 N195 + K393 A263 + Q345 T5 + N270 W48 + L173 A60 + S280T134 + D337 N195 + Q395 A263 + G346 T5 + G273 W48 + A174 A60 + T285T134 + Q345 G196 + A204 A263 + G348 T5 + S280 W48 + G184 A60 + M286T134 + G346 G196 + V206 A263 + T355 T5 + T285 W48 + T193 A60 + F289T134 + G348 G196 + P211 A263 + S376 T5 + M286 W48 + N195 A60 + V291T134 + T355 G196 + I214 A263 + D377 T5 + F289 W48 + G196 A60 + Q299T134 + S376 G196 + V215 A263 + D379 T5 + V291 W48 + A204 A60 + S304T134 + D377 G196 + L217 A263 + Y382 T5 + Q299 W48 + V206 A60 + R320T134 + D379 G196 + L219 A263 + S383 T5 + S304 W48 + P211 A60 + H321T134 + Y382 G196 + L228 A263 + Q385 T5 + R320 W48 + I214 A60 + S323T134 + S383 G196 + L235 A263 + K391 T5 + H321 W48 + V215 A60 + H324T134 + Q385 G196 + V238 A263 + K393 T5 + S323 W48 + L217 A60 + F328T134 + K391 G196 + M246 A263 + Q395 T5 + H324 W48 + L219 A60 + T334T134 + K393 G196 + M248 V264 + A265 T5 + F328 W48 + L228 A60 + D337T134 + Q395 G196 + L250 V264 + Y267 T5 + T334 W48 + L235 A60 + Q345W140 + G142 G196 + G255 V264 + N270 T5 + D337 W48 + V238 A60 + G346W140 + G149 G196 + Q256 V264 + G273 T5 + Q345 W48 + M246 A60 + G348W140 + T165 G196 + A263 V264 + S280 T5 + G346 W48 + M248 A60 + T355W140 + W167 G196 + V264 V264 + T285 T5 + G348 W48 + L250 A60 + S376W140 + R171 G196 + A265 V264 + M286 T5 + T355 W48 + G255 A60 + D377W140 + Q172 G196 + Y267 V264 + F289 T5 + S376 W48 + Q256 A60 + D379W140 + L173 G196 + N270 V264 + V291 T5 + D377 W48 + A263 A60 + Y382W140 + A174 G196 + G273 V264 + Q299 T5 + D379 W48 + V264 A60 + S383W140 + G184 G196 + S280 V264 + S304 T5 + Y382 W48 + A265 A60 + Q385W140 + T193 G196 + T285 V264 + R320 T5 + S383 W48 + Y267 A60 + K391W140 + N195 G196 + M286 V264 + H321 T5 + Q385 W48 + N270 A60 + K393W140 + G196 G196 + F289 V264 + S323 T5 + K391 W48 + G273 A60 + Q395W140 + A204 G196 + V291 V264 + H324 T5 + K393 W48 + S280 K72 + R87W140 + V206 G196 + Q299 V264 + F328 T5 + Q395 W48 + T285 K72 + Q98W140 + P211 G196 + S304 V264 + T334 G7 + Q11 W48 + M286 K72 + M105W140 + I214 G196 + R320 V264 + D337 G7 + N16 W48 + F289 K72 + G109W140 + V215 G196 + H321 V264 + Q345 G7 + V17 W48 + V291 K72 + F113W140 + L217 G196 + S323 V264 + G346 G7 + Q32 W48 + Q299 K72 + R116W140 + L219 G196 + H324 V264 + G348 G7 + A37 W48 + S304 K72 + Q118W140 + L228 G196 + F328 V264 + T355 G7 + T40 W48 + R320 K72 + Q125W140 + L235 G196 + T334 V264 + S376 G7 + P45 W48 + H321 K72 + G133W140 + V238 G196 + D337 V264 + D377 G7 + W48 W48 + S323 K72 + T134W140 + M246 G196 + Q345 V264 + D379 G7 + G50 W48 + H324 K72 + W140W140 + M248 G196 + G346 V264 + Y382 G7 + T51 W48 + F328 K72 + G142W140 + L250 G196 + G348 V264 + S383 G7 + N54 W48 + T334 K72 + G149W140 + G255 G196 + T355 V264 + Q385 G7 + V56 W48 + D337 K72 + T165W140 + Q256 G196 + S376 V264 + K391 G7 + A60 W48 + Q345 K72 + W167W140 + A263 G196 + D377 V264 + K393 G7 + K72 W48 + G346 K72 + R171W140 + V264 G196 + D379 V264 + Q395 G7 + R87 W48 + G348 K72 + Q172W140 + A265 G196 + Y382 A265 + Y267 G7 + Q98 W48 + T355 K72 + L173W140 + Y267 G196 + S383 A265 + N270 G7 + M105 W48 + S376 K72 + A174W140 + N270 G196 + Q385 A265 + G273 G7 + G109 W48 + D377 K72 + G184W140 + G273 G196 + K391 A265 + S280 G7 + F113 W48 + D379 K72 + T193W140 + S280 G196 + K393 A265 + T285 G7 + R116 W48 + Y382 K72 + N195W140 + T285 G196 + Q395 A265 + M286 G7 + Q118 W48 + S383 K72 + G196W140 + M286 A204 + V206 A265 + F289 G7 + Q125 W48 + Q385 K72 + A204W140 + F289 A204 + P211 A265 + V291 G7 + G133 W48 + K391 K72 + V206W140 + V291 A204 + I214 A265 + Q299 G7 + T134 W48 + K393 K72 + P211W140 + Q299 A204 + V215 A265 + S304 G7 + W140 W48 + Q395 K72 + I214W140 + S304 A204 + L217 A265 + R320 G7 + G142 G50 + T51 K72 + V215W140 + R320 A204 + L219 A265 + H321 G7 + G149 G50 + N54 K72 + L217W140 + H321 A204 + L228 A265 + S323 G7 + T165 G50 + V56 K72 + L219W140 + S323 A204 + L235 A265 + H324 G7 + W167 G50 + A60 K72 + L228W140 + H324 A204 + V238 A265 + F328 G7 + R171 G50 + K72 K72 + L235W140 + F328 A204 + M246 A265 + T334 G7 + Q172 G50 + R87 K72 + V238W140 + T334 A204 + M248 A265 + D337 G7 + L173 G50 + Q98 K72 + M246W140 + D337 A204 + L250 A265 + Q345 G7 + A174 G50 + M105 K72 + M248W140 + Q345 A204 + G255 A265 + G346 G7 + G184 G50 + G109 K72 + L250W140 + G346 A204 + Q256 A265 + G348 G7 + T193 G50 + F113 K72 + G255W140 + G348 A204 + A263 A265 + T355 G7 + N195 G50 + R116 K72 + Q256W140 + T355 A204 + V264 A265 + S376 G7 + G196 G50 + Q118 K72 + A263W140 + S376 A204 + A265 A265 + 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Q169 A60 + V326 G184 + K269 G133 + V326W167 + V326 Q172 + A186 R116 + A186 K72 + Q169 G184 + W284 T134 + Q169Q169 + A186 Q172 + E190 R116 + E190 K72 + A186 G184 + Y295 T134 + A186Q169 + E190 Q172 + A225 R116 + A225 K72 + E190 G184 + V326 T134 + E190Q169 + L173 Q172 + K242 R116 + K242 K72 + A225 A186 + E190 T134 + A225Q169 + A174 Q172 + S244 R116 + S244 K72 + K242 A186 + T193 T134 + K242Q169 + G184 Q172 + N260 R116 + N260 K72 + S244 A186 + N195 T134 + S244Q169 + T193 Q172 + K269 R116 + K269 K72 + N260 A186 + G196 T134 + N260Q169 + N195 Q172 + W284 R116 + W284 K72 + K269 A186 + A204 T134 + K269Q169 + G196 Q172 + Y295 R116 + Y295 K72 + W284 A186 + V206 T134 + W284Q169 + A204 Q172 + V326 R116 + V326 K72 + Y295 A186 + P211 T134 + Y295Q169 + V206 L173 + A186 Q118 + Q169 K72 + V326 A186 + I214 T134 + V326Q169 + P211 L173 + E190 Q118 + A186 R87 + Q169 A186 + V215 W140 + Q169Q169 + I214 L173 + A225 Q118 + A225 R87 + A186 A186 + L217 W140 + A186Q169 + V215 L173 + K242 Q118 + K242 R87 + E190 A186 + L219 W140 + E190Q169 + L217 L173 + S244 Q118 + S244 R87 + A225 A186 + A225 W140 + A225Q169 + L219 L173 + N260 Q118 + N260 R87 + K242 A186 + L228 W140 + K242Q169 + A225 L173 + K269 Q118 + K269 R87 + S244 A186 + L235 W140 + S244Q169 + L228 L173 + W284 Q118 + W284 R87 + N260 A186 + V238 W140 + N260Q169 + L235 L173 + Y295 Q118 + Y295 R87 + K269 A186 + K242 W140 + K269Q169 + V238 L173 + V326 Q118 + V326 R87 + W284 A186 + S244 W140 + W284Q169 + K242 A174 + A186 Q125 + Q169 R87 + Y295 A186 + M246 W140 + Y295Q169 + S244 A174 + E190 Q125 + A186 R87 + V326 A186 + M248 W140 + V326Q169 + M246 A174 + A225 Q125 + E190 Q98 + Q169 A186 + L250 G142 + Q169Q169 + M248 A174 + K242 Q125 + A225 Q98 + A186 A186 + G255 G142 + A186Q169 + L250 A174 + S244 Q125 + K242 Q98 + E190 A186 + Q256 G142 + E190Q169 + G255 A174 + N260 Q125 + S244 Q98 + A225 A186 + N260 G142 + A225Q169 + Q256 A174 + K269 Q125 + N260 Q98 + K242 A186 + A263 G142 + K242Q169 + N260 A174 + W284 Q125 + K269 Q98 + S244 A186 + V264 G142 + S244Q169 + A263 A174 + Y295 Q125 + W284 Q98 + N260 A186 + A265 G142 + N260Q169 + V264 A174 + V326 Q125 + Y295 Q98 + K269 A186 + Y267 G142 + K269Q169 + A265 T193 + A225 Q125 + V326 Q98 + W284 A186 + K269 G142 + W284Q169 + Y267 T193 + K242 V215 + A225 Q98 + Y295 A186 + N270 G142 + Y295Q169 + K269 T193 + S244 V215 + K242 Q98 + V326 A186 + G273 G142 + V326Q169 + N270 T193 + N260 V215 + S244 M105 + Q169 A186 + S280 G149 + Q169Q169 + G273 T193 + K269 V215 + N260 M105 + A186 A186 + W284 G149 + A186Q169 + S280 T193 + W284 V215 + K269 M105 + E190 A186 + T285 G149 + E190Q169 + W284 T193 + Y295 V215 + W284 M105 + A225 A186 + M286 G149 + A225Q169 + T285 T193 + V326 V215 + Y295 M105 + K242 A186 + F289 G149 + K242Q169 + M286 N195 + A225 V215 + V326 M105 + S244 A186 + V291 G149 + S244Q169 + F289 N195 + K242 L217 + A225 M105 + N260 A186 + Y295 G149 + N260Q169 + V291 N195 + S244 L217 + K242 M105 + K269 A186 + Q299 G149 + K269Q169 + Y295 N195 + N260 L217 + S244 M105 + W284 A186 + S304 G149 + W284Q169 + Q299 N195 + K269 L217 + N260 M105 + Y295 A186 + R320 G149 + Y295Q169 + S304 N195 + W284 L217 + K269 M105 + V326 A186 + H321 G149 + V326Q169 + R320 N195 + Y295 L217 + W284 A225 + L228 A186 + S323 T165 + Q169Q169 + H321 N195 + V326 L217 + Y295 A225 + L235 A186 + H324 T165 + A186Q169 + S323 G196 + A225 L217 + V326 A225 + V238 A186 + V326 T165 + E190Q169 + H324 G196 + K242 L219 + A225 A225 + K242 A186 + F328 T165 + A225Q169 + V326 G196 + K242 L219 + K242 A225 + S244 A186 + T334 T165 + K242Q169 + F328 G196 + S244 L219 + S244 A225 + M246 A186 + D337 T165 + S244Q169 + T334 G196 + N260 L219 + N260 A225 + M248 A186 + Q345 T165 + N260Q169 + D337 G196 + K269 L219 + K269 A225 + L250 A186 + G346 T165 + K269Q169 + Q345 G196 + W284 L219 + W284 A225 + G255 A186 + G348 T165 + W284Q169 + G346 G196 + Y295 L219 + Y295 A225 + Q256 A186 + T355 T165 + Y295Q169 + G348 G196 + V326 L219 + V326 A225 + N260 A186 + S376 T165 + V326Q169 + T355 A204 + A225 M246 + N260 A225 + A263 A186 + D377 L228 + K242Q169 + S376 A204 + K242 M246 + K269 A225 + V264 A186 + D379 L228 + S244Q169 + D377 A204 + S244 M246 + W284 A225 + A265 A186 + Y382 L228 + N260Q169 + D379 A204 + N260 M246 + Y295 A225 + Y267 A186 + S383 L228 + K269Q169 + Y382 A204 + K269 M246 + V326 A225 + K269 A186 + Q385 L228 + W284Q169 + S383 A204 + W284 M248 + N260 A225 + N270 A186 + K391 L228 + Y295Q169 + Q385 A204 + Y295 M248 + K269 A225 + G273 A186 + K393 L228 + V326Q169 + K391 A204 + V326 M248 + W284 A225 + S280 A186 + Q395 L235 + K242Q169 + K393 V206 + A225 M248 + Y295 A225 + W284 E190 + T193 L235 + S244Q169 + Q395 A206 + K242 M248 + V326 A225 + T285 E190 + N195 L235 + N260Q256 + N260 A206 + S244 L250 + N260 A225 + M286 E190 + G196 L235 + K269G256 + K269 A206 + N260 L250 + K269 A225 + F289 E190 + A204 L235 + W284Q256 + W284 A206 + K269 L250 + W284 A225 + V291 E190 + V206 L235 + Y295Q256 + Y295 A206 + W284 L250 + Y295 A225 + Y295 E190 + P211 L235 + V326Q256 + V326 A206 + Y295 L250 + V326 A225 + Q299 E190 + I214 V238 + K242N260 + A263 A206 + V326 G255 + N260 A225 + S304 E190 + V215 V238 + S244N260 + V264 P211 + A225 G255 + K269 A225 + R320 E190 + L217 V238 + N260N260 + A265 P211 + K242 G255 + W284 A225 + H321 E190 + L219 V238 + K269N260 + Y267 P211 + S244 G255 + Y295 A225 + S323 E190 + A225 V238 + W284N260 + K269 P211 + N206 G255 + V326 A225 + H324 E190 + L228 V238 + Y295N260 + N270 P211 + K269 N270 + W284 A225 + V326 E190 + L235 V238 + V326N260 + G273 P211 + W284 N270 + Y295 A225 + F328 E190 + V238 K242 + S244N260 + S280 P211 + Y295 N270 + V326 A225 + T334 E190 + K242 K242 + M246N260 + W284 P211 + V326 G273 + W284 A225 + D337 E190 + S244 K242 + M248N260 + T285 I214 + A225 G273 + Y295 A225 + Q345 E190 + M246 K242 + L250N260 + M286 I214 + K242 G273 + V326 A225 + G346 E190 + M248 K242 + G255N260 + F289 I214 + S244 S280 + W284 A225 + G348 E190 + L250 K242 + Q256N260 + V291 I214 + N260 S280 + Y295 A225 + T355 E190 + G255 K242 + N260N260 + Y295 I214 + K269 S280 + V326 A225 + S376 E190 + Q256 K242 + A263N260 + Q299 I214 + W284 W284 + T285 A225 + D377 E190 + N260 K242 + V264N260 + S304 I214 + Y295 W284 + M286 A225 + D379 E190 + A263 K242 + A265N260 + R320 I214 + V326 W284 + F289 A225 + Y382 E190 + V264 K242 + Y267N260 + H321 K269 + N270 W284 + V291 A225 + S383 E190 + A265 K242 + K269N260 + S323 K269 + G273 W284 + Y295 A225 + Q385 E190 + Y267 K242 + N270N260 + H324 K269 + S280 W284 + Q299 A225 + K391 E190 + K269 K242 + G273N260 + V326 K269 + W284 W284 + S304 A225 + K393 E190 + N270 K242 + S280N260 + F328 K269 + T285 W284 + R320 A225 + Q395 E190 + G273 K242 + W284N260 + T334 K269 + M286 W284 + H321 A263 + K269 E190 + S280 K242 + T285N260 + D337 K269 + F289 W284 + S323 A263 + W284 E190 + W284 K242 + M286N260 + Q345 K269 + V291 W284 + H324 A263 + Y295 E190 + T285 K242 + F289N260 + G346 K269 + Y295 W284 + V326 A263 + V326 E190 + M286 K242 + V291N260 + G348 K269 + Q299 W284 + F328 V264 + K269 E190 + F289 K242 + Y295N260 + T355 K269 + S304 W284 + T334 V264 + W284 E190 + V291 K242 + Q299N260 + S376 K269 + R320 W284 + D337 V264 + Y295 E190 + Y295 K242 + S304N260 + D377 K269 + H321 W284 + Q345 V264 + V326 E190 + Q299 K242 + R320N260 + D379 K269 + S323 W284 + G346 A265 + K269 E190 + S304 K242 + H321N260 + Y382 K269 + H324 W284 + G348 A265 + W284 E190 + R320 K242 + S323N260 + S383 K269 + V326 W284 + T355 A265 + Y295 E190 + H321 K242 + H324N260 + Q385 K269 + F328 W284 + S376 A265 + V326 E190 + S323 K242 + V326N260 + K391 K269 + T334 W284 + D377 A265 + K269 E190 + H324 K242 + F328N260 + K393 K269 + D337 W284 + D379 A265 + W284 E190 + V326 K242 + T334N260 + Q395 K269 + Q345 W284 + Y382 A265 + Y295 E190 + F328 K242 + D337Y295 + S376 K269 + G346 W284 + S383 A265 + V326 E190 + T334 K242 + Q345V326 + S376 K269 + G348 W284 + Q385 Y295 + D377 E190 + D337 K242 + G346V326 + D377 K269 + T355 W284 + K391 Y295 + D379 E190 + Q345 K242 + G348V326 + D379 K269 + S376 W284 + K393 Y295 + Y382 E190 + G346 K242 + T355V326 + Y382 K269 + D377 W284 + Q395 Y295 + S383 E190 + G348 K242 + S376V326 + S383 K269 + D379 T285 + Y295 Y295 + Q385 E190 + T355 K242 + D377V326 + Q385 K269 + Y382 T285 + V326 Y295 + K391 E190 + S376 K242 + D379V326 + K391 K269 + S383 M286 + Y295 Y295 + K393 E190 + D377 K242 + Y382V326 + K393 K269 + Q385 M286 + V326 Y295 + Q395 E190 + D379 K242 + S383V326 + Q395 K269 + K391 F289 + Y295 Q299 + V326 E190 + Y382 K242 + Q385S244 + K393 K269 + K393 F289 + V326 S304 + V326 E190 + S383 K242 + K391S244 + Q395 K269 + Q395 V291 + Y295 R320 + V326 E190 + Q385 K242 + K393S244 + Y267 S244 + R320 V294 + V326 H321 + V326 E190 + K391 K242 + Q395S244 + K269 S244 + H321 Y295 + Q299 S323 + V326 E190 + K393 S244 + M246S244 + N270 S244 + S323 Y295 + S304 H324 + V326 E190 + Q395 S244 + M248S244 + G273 S244 + H324 Y295 + R320 V326 + F328 S244 + F289 S244 + L250S244 + S280 S244 + V326 Y295 + H321 V326 + T334 S244 + V291 S244 + G255S244 + W284 S244 + F328 Y295 + S323 V326 + D337 S244 + Y295 S244 + Q256S244 + T285 S244 + T334 Y295 + H324 V326 + Q345 S244 + Q299 S244 + N260S244 + S376 S244 + D337 Y295 + V326 V326 + G346 S244 + S304 S244 + A263S244 + D377 S244 + Q345 Y295 + F328 V326 + G348 S244 + K391 S244 + V264S244 + D379 S244 + G346 Y295 + T334 V326 + T355 S244 + M286 S244 + A265S244 + Y382 S244 + G348 Y295 + F328 Y295 + G348 Y295 + Q345 S244 + S383S244 + T355 Y295 + T334 Y295 + T355 Y295 + G346 S244 + Q385 Y295 + D337

In one particular embodiment, the modifications in one or more positionscorrespond to the following; H1*, T5K, G7K, G7A, Q11H, N16S, N16H, V17L,Q323, A37H, A37M, A37V, A373, A37Y, A37R, A37L, T40D, T40G, T40K, P45A,W48G, W48Y, W48F, G50A, T51K, T51E, T51G, T51A, T51S, T51G, T51D, N54S,V56T, A60V, K72R, K72H, K72S, K72Q, K72E, K72N, K72A, K72M, R87S, Q983,Q98A, M105F, M105I, M105V, M105L, G109A, G109S, F113W, F113S, F113N,F113Y, F113R, F113L, F113Q, R116Q, R116V, R116K, R116W, R116L, R116A,R116H, R116M, R116E, R116S, R116I, R116G, Q118N, Q118K, Q118G, Q118S,Q118F, Q118R, Q125P, Q125K, Q125A, Q125T, N125D, G133S, F133Q, T134E,W140Y, G142T, G149Q, T165S, T165G, T165V, W167I, W167G, W167F, W167R,W167S, W167H, W167L, W167M, W167Y, Q169E, R171H, Q172G, Q172R, Q172N,Q172D, Q172Y, Q172M, Q172S, Q172T, Q172K, Q172H, Q172E, L173V, L173G,L173H, L173A, L173I, L173P, L173T, L173F, L173M, A174S, A174D, A174P,A174M, A174T, A174H, A174K, A174G, A174Q, A174N, A174V, A174L, G184T,A186D, A186N, A186E, A186Q, A186H, E190P, T193K, N195F, G196R, A204T,A204V, A204S, A204G, V206L, V206S, V206Y, P211D, I214G, I214H, I214S,214T, I214L, I214E, I214W, V215T, L217T, L217Q, L219V, L219H, A225V,L228I, L235V, L235A, V238A, V238T, V238G, K242Q, S244Q, M246L, M246A,M246I, M246F, M246V, M246S, M248T, L250I, L250V, L250T, L250A, L250F,L250M, G255N, G255A, G255A, Q256A, N260G, A263G, V264I, V264T, A265G,Y267I, Y267M, Y267H, Y267L, K269Q, N270G, N270I, G273R, S280W, S280L,S280T, S280A, S280K, S280Q, W284H, T285L, T285Q, M286F, M286L, A288L,A288V, F289I, F289L, V291G, V291A, V291T, Y295N, Y295F, Q299V, S304N,S304R, R320A, R320V, H321Y, S323N, H324L, V326L, F328L, F328M, F328V,F328I, T334S, D337H, Q345D, G346T, G346D, G346P, G348S, G348P, T355L,T355F, S376H, S376I, S376V, D377H, D377S, D377A, D377Q, D379S, D379G,D379R, D379A, Y382M, Y382I, Y382L, Y382F, S383G, S383A, Q385L, K391A,K391Y, K391V, K391M, K391E, K391D, K391R, K391H, K391W, K391I, K391Q,K391L, K393Y, K393R, K393Q, K393S, and Q395P, wherein said positionscorrespond to positions of SEQ ID NOs: 7 or 10.

The inventors of the present invention have identified that thesespecific alterations within the A and B domain (as defined by SEQ ID NO:10) of the amino acid sequence as set forth in SEQ ID NOs: 7 and 10, areparticularly relevant for improving the performance of a variantalpha-amylase having at least 65% sequence identity to the parentpolypeptide.

In one embodiment, the variant comprises an alteration in two, three,four, five, six, seven, eight, nine, ten, eleven, twelf, thirteen,fourteen, fifteen, sixteen, or seventeen positions corresponding to thefollowing positions: H1*, T5K, G7K, G7A, Q11H, N16S, N16H, V17L, Q32S,A37H, A37M, A37V, A37S, A37Y, A37R, A37L, T40D, T40G, T40K, P45A, W48G,W48Y, W48F, G50A, T51K, T51E, T51G, T51A, T51S, T51G, T51D, N54S, V56T,A60V, K72R, K72H, K72S, K72Q, K72E, K72N, K72A, K72M, R87S, Q98S, Q98A,M105F, M105I, M105V, M105L, G109A, G109S, F113W, F113S, F113N, F113Y,F113R, F113L, F113Q, R116Q, R116V, R116K, R116W, R116L, R116A, R116H,R116M, R116E, R116S, S116I, R116G, Q118N, Q118K, Q118G, Q118S, Q118F,Q118R, Q125P, Q125K, Q125A, Q125T, N125D, G133S, F133Q, T134E, W140Y,G142T, G149Q, T165S, T165G, I165V, W167I, W167G, W167F, W167R, W167S,W167H, W167L, W167M, W167Y, Q169E, R171H, Q172G, Q172R, Q172N, Q172D,Q172Y, Q172M, Q172S, Q172I, Q172K, Q172H, Q172E, L173V, L173G, L173H,L173A, L173I, L173P, L173T, L173F, L173M, A174S, A174D, A174P, A174M,A174T, A174H, A174K, A174G, A174Q, A174N, A174V, A174L, G184I, A186D,A186N, A186E, A186Q, A186H, E190P, T193K, N195F, G196R, A204T, A204V,A204S, A204G, V206L, V206S, V206Y, P211D, I214G, I214H, I214S, I214T,I214L, I214E, I214W, V215T, L217T, L217Q, L219V, L219H, A225V, L228I,L235V, L235A, V238A, V238T, V238G, K242Q, S244Q, M246L, M246A, M246I,M246F, M246V, M246S, M248T, L250I, L250V, L250T, L250A, L250F, L250M,G255N, G255A, G255S, Q256A, N260G, A263G, V264I, V264T, A265G, Y267I,Y267M, Y267H, Y267L, K269Q, N270G, N270T, G273R, S280W, S280L, S280T,S280A, S280K, S280Q, W284H, T285L, T285Q, M286F, M286L, A288L, A288V,F289I, F289L, V291G, V291A, V291T, Y295N, Y295F, Q299V, S304N, S304R,R320A, R320V, H321Y, S323N, H324L, V326L, F328L, F328M, F328V, F328I,T334S, D337H, Q345D, G346T, G346D, G346P, G348S, G348P, T355L, T355F,S376H, S376T, S376V, D377H, D377S, D377A, D377Q, D379S, D379G, D379R,D379A, Y382M, Y382I, Y382L, Y382F, S383G, S383A, Q385L, K391A, K391Y,K391V, K391M, K391E, K391D, K391R, K391H, K391W, K391I, K391Q, K391L,K393Y, K393R, K393Q, K393S, and Q395P, wherein said positions correspondto positions of SEQ ID NOs: 7 or 10.

The C domain of a variant according to the present invention may alsocomprise alterations. Thus, in one embodiment, the variant comprises analteration in one or more amino acid positions corresponding to theamino acid positions of the amino acid sequence set forth in SEQ ID NOs:11 or 12, or an amino acid sequence having at least 65% sequenceidentity to an amino acid sequence as set forth in SEQ ID NOs: 11 or 12.

In one particular embodiment, the C domain comprises an alteration inone or more of the following positions corresponding to positions; A420,G423, T444, A445, Q449, T459, P473, C474, G476, G477, and K484 of SEQ1DNO: 13 or I405, A421, A422, A428, R439 G448, W467, D476, and G477 of SEQID NO: 14.

In one embodiment, the variant comprises an alteration in two, three,four, five, six, seven, or eight positions corresponding to thefollowing positions; A420, G423, T444, A445, Q449, T459, P473, C474,G476, G477, and K484 of SEQ ID NO: 13 or I405, A421, A422, A428, R439G448, W467, D476, and G477 of SEQ ID NO: 14.

The inventors of the present invention have identified that specificamino acid substitutions within the C domain of parent polypeptide havean improved effect on performance of the variants. Thus, in a particularembodiment, the alteration in one or more positions correspond to thefollowing T400P, H402R, A420Q, A420S, A420K, A420L, G423H, T444Q, T444S,T444D, T444Y, T444H, T444V, T444R, T444A, A445Q, Q449T, T459N, P473R,P473A, P473G, P473T, P473K, C474V, G476K, G477A, G477Q, K484A, K484G,K484P, K484E, K484Q, and K484S, wherein said positions correspond topositions of SEQ ID NO: 13; or I405L. A421H, A422P, A428T, G448D, D476K,D476G, D476N, D476Y, G477S, G477A, G477T, and G477Q, wherein saidpositions correspond to positions of SEQ ID NO: 14.

In a particular embodiment, the variant comprises a modification in thefollowing positions;

H1 + T5 T40 + A174 R87 + N270 W140 + K393 V206 + V215 Y267 + C474 H1 +G7 T40 + G184 R87 + G273 W140 + Q395 V206 + L217 Y267 + G476 H1 + Q11T40 + T193 R87 + S280 W140 + A420 V206 + L219 Y267 + G477 H1 + N16 T40 +N195 R87 + T285 W140 + G423 V206 + L235 Y267 + K484 H1 + V17 T40 + A204R87 + M286 W140 + T444 V206 + V238 N270 + G273 H1 + Q32 T40 + V206 R87 +F289 W140 + A445 V206 + M246 N270 + S280 H1 + A37 T40 + P211 R87 + V291W140 + Q449 V206 + M248 N270 + T285 H1 + T40 T40 + I214 R87 + Q299W140 + T459 V206 + L250 N270 + M286 H1 + P45 T40 + V215 R87 + R320W140 + P473 V206 + G255 N270 + F289 H1 + W48 T40 + L217 R87 + H321W140 + C474 V206 + Q256 N270 + V291 H1 + G50 T40 + L219 R87 + S323W140 + G476 V206 + A263 N270 + Q299 H1 + T51 T40 + L235 R87 + H324W140 + G477 V206 + V264 N270 + R320 H1 + N54 T40 + V238 R87 + F328W140 + K484 V206 + Y267 N270 + H321 H1 + V56 T40 + M246 R87 + T334G142 + G149 V206 + N270 N270 + S323 H1 + K72 T40 + M248 R87 + D337G142 + T165 V206 + G273 N270 + H324 H1 + R87 T40 + L250 R87 + Q345G142 + W167 V206 + S280 N270 + F328 H1 + Q98 T40 + G255 R87 + G346G142 + R171 V206 + T285 N270 + T334 H1 + M105 T40 + Q256 R87 + G348G142 + Q172 V206 + M286 N270 + D337 H1 + G109 T40 + A263 R87 + T355G142 + L173 V206 + F289 N270 + Q345 H1 + F113 T40 + V264 R87 + S376G142 + A174 V206 + V291 N270 + G346 H1 + R116 T40 + Y267 R87 + D377G142 + G184 V206 + Q299 N270 + G348 H1 + Q118 T40 + N270 R87 + D379G142 + T193 V206 + R320 N270 + T355 H1 + Q125 T40 + G273 R87 + Y382G142 + N195 V206 + H321 N270 + S376 H1 + G133 T40 + S280 R87 + S383G142 + A204 V206 + S323 N270 + D377 H1 + T134 T40 + T285 R87 + Q385G142 + V206 V206 + H324 N270 + D379 H1 + W140 T40 + M286 R87 + K391G142 + P211 V206 + F328 N270 + Y382 H1 + G142 T40 + F289 R87 + K393G142 + I214 V206 + T334 N270 + S383 H1 + G149 T40 + V291 R87 + Q395G142 + V215 V206 + D337 N270 + Q385 H1 + T165 T40 + Q299 R87 + A420G142 + L217 V206 + Q345 N270 + K391 H1 + W167 T40 + R320 R87 + G423G142 + L219 V206 + G346 N270 + K393 H1 + 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G348 A204 + Q449Y267 + G423 T459 + G476 T40 + W140 V17 + E190 W140 + T355 A204 + T459Y267 + T444 T459 + G477 T40 + G142 V17 + A225 W140 + S376 A204 + P473Y267 + A445 T459 + K484 T40 + G149 V17 + K242 W140 + D377 A204 + C474Y267 + Q449 P473 + C474 T40 + T165 V17 + S244 W140 + D379 A204 + G476Y267 + T459 P473 + G476 T40 + W167 V17 + G258 W140 + Y382 A204 + G477Y267 + P473 P473 + G477 T40 + R171 V17 + N260 W140 + S383 A204 + K484G109 + Q169 P473 + K484 T40 + Q172 V17 + K269 W140 + Q385 V206 + P211G109 + A186 C474 + G476 T40 + L173 V17 + W284 W140 + K391 V206 + I214G109 + E190 C474 + G477 T40 + Q169 V17 + Y295 N54 + Q169 K72 + Q169G109 + A225 C474 + K484 T40 + A186 V17 + S304 N54 + A186 K72 + A186G109 + K242 G476 + G477 T40 + E190 V17 + V326 N54 + E190 K72 + E190G109 + S244 G476 + K484 T40 + A225 Q32 + Q169 N54 + A225 K72 + A225G109 + G258 G477 + K484 T40 + K242 Q32 + A186 N54 + K242 K72 + K242G109 + N260 G133 + Q169 T40 + S244 Q32 + E190 N54 + S244 K72 + S244G109 + K269 G133 + A186 T40 + G258 Q32 + A225 N54 + G258 K72 + G258G109 + W284 G133 + E190 T40 + N260 Q32 + K242 N54 + N260 K72 + N260G109 + Y295 G133 + A225 T40 + K269 Q32 + S244 N54 + K269 K72 + K269G109 + S304 G133 + K242 T40 + W284 Q32 + G258 N54 + W284 K72 + W284G109 + V326 G133 + S244 T40 + Y295 Q32 + N260 N54 + Y295 K72 + Y295F113 + Q169 G133 + G258 T40 + S304 Q32 + K269 N54 + S304 K72 + S304F113 + A186 G133 + N260 T40 + V326 Q32 + W284 N54 + V326 K72 + V326F113 + E190 G133 + K269 P45 + Q169 Q32 + Y295 V56 + Q169 R87 + Q169F113 + A225 G133 + W284 P45 + A186 Q32 + S304 V56 + A186 R87 + A186F113 + K242 G133 + Y295 P45 + E190 Q32 + V326 V56 + E190 R87 + E190F113 + S244 G133 + S304 P45 + A225 A37 + Q169 V56 + A225 R87 + A225F113 + G258 G133 + V326 P45 + K242 A37 + A186 V56 + K242 R87 + K242F113 + N260 T134 + Q169 P45 + S244 A37 + E190 V56 + S244 R87 + S244F113 + K269 T134 + A186 P45 + G258 A37 + A225 V56 + G258 R87 + G258F113 + W284 T134 + E190 P45 + N260 A37 + K242 V56 + N260 R87 + N260F113 + Y295 T134 + A225 P45 + K269 A37 + S244 V56 + K269 R87 + K269F113 + S304 T134 + K242 P45 + W284 A37 + G258 V56 + W284 R87 + W284F113 + V326 T134 + S244 P45 + Y295 A37 + N260 V56 + Y295 R87 + Y295R116 + Q169 T134 + G258 P45 + S304 A37 + K269 V56 + S304 R87 + S304R116 + A186 T134 + N260 P45 + V326 A37 + W284 V56 + V326 R87 + V326R116 + E190 T134 + K269 W48 + Q169 A37 + Y295 Q169 + R171 Q98 + Q169R116 + A225 T134 + W284 W48 + A186 A37 + S304 Q169 + Q172 Q98 + A186R116 + K242 T134 + Y295 W48 + E190 A37 + V326 Q169 + L173 Q98 + E190R116 + S244 T134 + S304 W48 + A225 G142 + Q169 Q169 + A174 Q98 + A225R116 + G258 T134 + V326 W48 + K242 G142 + A186 Q169 + G184 Q98 + K242R116 + N260 W140 + Q169 W48 + S244 G142 + E190 Q169 + A186 Q98 + S244R116 + K269 W140 + A186 W48 + G258 G142 + A225 Q169 + E190 Q98 + G258R116 + W284 W140 + E190 W48 + N260 G142 + K242 Q169 + T193 Q98 + N260R116 + Y295 W140 + A225 W48 + K269 G142 + S244 Q169 + N195 Q98 + K269R116 + S304 W140 + K242 W48 + W284 G142 + G258 Q169 + A204 Q98 + W284R116 + V326 W140 + S244 W48 + Y295 G142 + N260 Q169 + V206 Q98 + Y295Q118 + Q169 W140 + G258 W48 + S304 G142 + K269 Q169 + P211 Q98 + S304Q118 + A186 W140 + N260 W48 + V326 G142 + W284 Q169 + I214 Q98 + V326Q118 + E190 W140 + K269 G50 + Q169 G142 + Y295 Q169 + V215 M105 + Q169Q118 + A225 W140 + W284 G50 + A186 G142 + S304 Q169 + L217 M105 + A186Q118 + K242 W140 + Y295 G50 + E190 G142 + V326 Q169 + L219 M105 + E190Q118 + S244 W140 + S304 G50 + A225 G149 + Q169 Q169 + A225 M105 + A225Q118 + G258 W140 + V326 G50 + K242 G149 + A186 Q169 + L235 M105 + K242Q118 + N260 E190 + L235 G50 + S244 G149 + E190 Q169 + V238 M105 + S244Q118 + K269 A225 + V238 G50 + G258 G149 + A225 Q169 + K242 M105 + G258Q118 + W284 A225 + K242 G50 + N260 G149 + K242 Q169 + S244 M105 + N260Q118 + Y295 A225 + S244 G50 + K269 G149 + S244 Q169 + M246 M105 + K269Q118 + S304 A225 + M246 G50 + W284 G149 + G258 Q169 + M248 M105 + W284Q118 + V326 A225 + M248 G50 + Y295 G149 + N260 Q169 + L250 M105 + Y295Q125 + Q169 A225 + L250 G50 + S304 G149 + K269 Q169 + G255 M105 + S304Q125 + A186 A225 + G255 G50 + V326 G149 + W284 Q169 + Q256 M105 + V326Q125 + E190 A225 + Q256 T51 + Q169 G149 + Y295 Q169 + G258 R171 + A186Q125 + A225 A225 + G258 T51 + A186 G149 + S304 Q169 + N260 R171 + E190Q125 + K242 A225 + N260 T51 + E190 G149 + V326 Q169 + A263 R171 + A225Q125 + S244 A225 + A263 T51 + A225 T165 + Q169 Q169 + V264 R171 + K242Q125 + G258 A225 + V264 T51 + K242 T165 + A186 Q169 + Y267 R171 + S244Q125 + N260 A225 + Y267 T51 + S244 T165 + E190 Q169 + K269 R171 + G258Q125 + K269 A225 + K269 T51 + G258 T165 + A225 Q169 + N270 R171 + N260Q125 + W284 A225 + N270 T51 + N260 T165 + K242 Q169 + G273 R171 + K269Q125 + Y295 A225 + G273 T51 + K269 T165 + S244 Q169 + S280 R171 + W284Q125 + S304 A225 + S280 T51 + W284 T165 + G258 Q169 + W284 R171 + Y295Q125 + V326 A225 + W284 T51 + Y295 T165 + N260 Q169 + T285 R171 + S304G184 + A186 A225 + T285 T51 + S304 T165 + K269 Q169 + M286 R171 + V326G184 + E190 A225 + M286 T51 + V326 T165 + W284 Q169 + F289 Q172 + A186G184 + A225 A225 + F289 A186 + E190 T165 + Y295 Q169 + V291 Q172 + E190G184 + K242 A225 + V291 A186 + T193 T165 + S304 Q169 + Y295 Q172 + A225G184 + S244 A225 + Y295 A186 + N195 T165 + V326 Q169 + Q299 Q172 + K242G184 + G258 A225 + Q299 A186 + A204 W167 + Q169 Q169 + S304 Q172 + S244G184 + N260 A225 + S304 A186 + V206 W167 + A186 Q169 + R320 Q172 + G258G184 + K269 A225 + R320 A186 + P211 W167 + E190 Q169 + H321 Q172 + N260G184 + W284 A225 + H321 A186 + I214 W167 + A225 Q169 + S323 Q172 + K269G184 + Y295 A225 + S323 A186 + V215 W167 + K242 Q169 + H324 Q172 + W284G184 + S304 A225 + H324 A186 + L217 W167 + S244 Q169 + V326 Q172 + Y295G184 + V326 A225 + V326 A186 + L219 W167 + G258 Q169 + F328 Q172 + S304L235 + K242 A225 + F328 A186 + A225 W167 + N260 Q169 + T334 Q172 + V326L235 + S244 A225 + T334 A186 + L235 W167 + K269 Q169 + D337 L173 + A186L235 + G258 A225 + D337 A186 + V238 W167 + W284 Q169 + Q345 L173 + E190L235 + N260 A225 + Q345 A186 + K242 W167 + Y295 Q169 + G346 L173 + A225L235 + K269 A225 + G346 A186 + S244 W167 + S304 Q169 + G348 L173 + K242L235 + W284 A225 + G348 A186 + M246 W167 + V326 Q169 + T355 L173 + S244L235 + Y295 A225 + T355 A186 + M248 E190 + T193 Q169 + S376 L173 + G258L235 + S304 A225 + S376 A186 + L250 E190 + N195 Q169 + D377 L173 + N260L235 + V326 A225 + D377 A186 + G255 E190 + A204 Q169 + D379 L173 + K269V238 + K242 A225 + D379 A186 + Q256 E190 + V206 Q169 + Y382 L173 + W284V238 + S244 A225 + Y382 A186 + G258 E190 + P211 Q169 + S383 L173 + Y295V238 + G258 A225 + S383 A186 + N260 E190 + I214 Q169 + Q385 L173 + S304V238 + N260 A225 + Q385 A186 + A263 E190 + V215 Q169 + K391 L173 + V326V238 + K269 A225 + K391 A186 + V264 E190 + L217 Q169 + K393 A174 + A186V238 + W284 A225 + K393 A186 + Y267 E190 + L219 Q169 + Q395 A174 + E190V238 + Y295 A225 + Q395 A186 + K269 E190 + A225 Q169 + A420 A174 + A225V238 + S304 A225 + A420 A186 + N270 E190 + L235 Q169 + G423 A174 + K242V238 + V326 A225 + G423 A186 + G273 E190 + V238 Q169 + T444 A174 + S244K242 + S244 A225 + T444 A186 + S280 E190 + K242 Q169 + A445 A174 + G258K242 + M246 A225 + A445 A186 + W284 E190 + S244 Q169 + Q449 A174 + N260K242 + M248 A225 + Q449 A186 + T285 E190 + M246 Q169 + T459 A174 + K269K242 + L250 A225 + T459 A186 + M286 E190 + M248 Q169 + P473 A174 + W284K242 + G255 A225 + P473 A186 + F289 E190 + L250 Q169 + C474 A174 + Y295K242 + Q256 A225 + C474 A186 + V291 E190 + G255 Q169 + G476 A174 + S304K242 + G258 A225 + G476 A186 + Y295 E190 + Q256 Q169 + G477 A174 + V326K242 + N260 A225 + G477 A186 + Q299 E190 + G258 Q169 + K484 L217 + A225K242 + A263 A225 + K484 A186 + S304 E190 + N260 T193 + A225 L217 + K242K242 + V264 S244 + M248 A186 + R320 E190 + A263 T193 + K242 L217 + S244K242 + Y267 S244 + L250 A186 + H321 E190 + V264 T193 + S244 L217 + G258K242 + K269 S244 + G255 A186 + S323 E190 + Y267 T193 + G258 L217 + N260K242 + N270 S244 + Q256 A186 + H324 E190 + K269 T193 + N260 L217 + K269K242 + G273 S244 + G258 A186 + V326 E190 + N270 T193 + K269 L217 + W284K242 + S280 S244 + N260 A186 + F328 E190 + G273 T193 + W284 L217 + Y295K242 + W284 S244 + A263 A186 + T334 E190 + S280 T193 + Y295 L217 + S304K242 + T285 S244 + V264 A186 + D337 E190 + W284 T193 + S304 L217 + V326K242 + M286 S244 + Y267 A186 + Q345 E190 + T285 T193 + V326 L219 + A225K242 + F289 S244 + K269 A186 + G346 E190 + M286 N195 + A225 L219 + K242K242 + V291 S244 + N270 A186 + G348 E190 + F289 N195 + K242 L219 + S244K242 + Y295 S244 + G273 A186 + T355 E190 + V291 N195 + S244 L219 + G258K242 + Q299 S244 + S280 A186 + S376 E190 + Y295 N195 + G258 L219 + N260K242 + S304 S244 + W284 A186 + D377 E190 + Q299 N195 + N260 L219 + K269K242 + R320 S244 + T285 A186 + D379 E190 + S304 N195 + K269 L219 + W284K242 + H321 S244 + M286 A186 + Y382 E190 + R320 N195 + W284 L219 + Y295K242 + S323 S244 + F289 A186 + S383 E190 + H321 N195 + Y295 L219 + S304K242 + H324 S244 + V291 A186 + Q385 E190 + S323 N195 + S304 L219 + V326K242 + V326 S244 + Y295 A186 + K391 E190 + H324 N195 + V326 M246 + G258K242 + F328 S244 + Q299 A186 + K393 E190 + V326 A204 + A225 M246 + N260K242 + T334 S244 + S304 A186 + Q395 E190 + F328 A204 + K242 M246 + K269K242 + D337 S244 + R320 A186 + A420 E190 + T334 A204 + S244 M246 + W284K242 + Q345 S244 + H321 A186 + G423 E190 + D337 A204 + G258 M246 + Y295K242 + G346 S244 + S323 A186 + T444 E190 + Q345 A204 + N260 M246 + S304K242 + G348 S244 + H324 A186 + A445 E190 + G346 A204 + K269 M246 + V326K242 + T355 S244 + V326 A186 + Q449 E190 + G348 A204 + W284 M248 + G258K242 + S376 S244 + F328 A186 + T459 E190 + T355 A204 + Y295 M248 + N260K242 + D377 S244 + T334 A186 + P473 E190 + S376 A204 + S304 M248 + K269K242 + D379 S244 + D337 A186 + C474 E190 + D377 A204 + V326 M248 + W284K242 + Y382 S244 + Q345 A186 + G476 E190 + D379 V206 + A225 M248 + Y295K242 + S383 S244 + G346 A186 + G477 E190 + Y382 V206 + K242 M248 + S304K242 + Q385 S244 + G348 A186 + K484 E190 + S383 V206 + S244 M248 + V326K242 + K391 S244 + T355 I214 + A225 E190 + Q385 V206 + G258 L250 + G258K242 + K393 S244 + S376 I214 + K242 E190 + K391 V206 + N260 L250 + N260K242 + Q395 S244 + D377 I214 + S244 E190 + K393 V206 + K269 L250 + K269K242 + A420 S244 + D379 I214 + G258 E190 + Q395 V206 + W284 L250 + W284K242 + G423 S244 + Y382 I214 + N260 E190 + A420 V206 + Y295 L250 + Y295K242 + T444 S244 + S383 I214 + K269 E190 + G423 V206 + S304 L250 + S304K242 + A445 S244 + Q385 I214 + W284 E190 + T444 V206 + V326 L250 + V326K242 + Q449 S244 + K391 I214 + Y295 E190 + A445 P211 + A225 G255 + G258K242 + T459 S244 + K393 I214 + S304 E190 + Q449 P211 + K242 G255 + N260K242 + P473 S244 + Q395 I214 + V326 E190 + T459 P211 + S244 G255 + K269K242 + C474 S244 + A420 V215 + A225 E190 + P473 P211 + G258 G255 + W284K242 + G476 S244 + G423 V215 + K242 E190 + C474 P211 + N260 G255 + Y295K242 + G477 S244 + T444 V215 + S244 E190 + G476 P211 + K269 G255 + S304K242 + K484 S244 + A445 V215 + G258 E190 + G477 P211 + W284 G255 + V326N260 + A263 S244 + Q449 V215 + N260 E190 + K484 P211 + Y295 Q256 + G258N260 + V264 S244 + T459 V215 + K269 G258 + N260 P211 + S304 Q256 + N260N260 + Y267 S244 + P473 V215 + W284 G258 + A263 P211 + V326 Q256 + K269N260 + K269 S244 + C474 V215 + Y295 G258 + V264 A236 + K269 Q256 + W284N260 + N270 S244 + G476 V215 + S304 G258 + Y267 A236 + W284 Q256 + Y295N260 + G273 S244 + G477 V215 + V326 G258 + K269 A236 + Y295 Q256 + S304N260 + S280 S244 + K484 N270 + W284 G258 + N270 A236 + S304 Q256 + V326N260 + W284 K269 + N270 N270 + Y295 G258 + G273 A236 + V326 W284 + T285N260 + T285 K269 + G273 N270 + S304 G258 + S280 V264 + K269 W284 + M286N260 + M286 K269 + S280 N270 + V326 G258 + W284 V264 + W284 W284 + F289N260 + F289 K269 + W284 G273 + W284 G258 + T285 V264 + Y295 W284 + V291N260 + V291 K269 + T285 G273 + Y295 G258 + M286 V264 + S304 W284 + Y295N260 + Y295 K269 + M286 G273 + S304 G258 + F289 V267 + V326 W284 + Q299N260 + Q299 K269 + F289 G273 + V326 G258 + V291 Y267 + K269 W284 + S304N260 + S304 K269 + V291 S280 + W284 G258 + Y295 Y267 + W284 W284 + R320N260 + R320 K269 + Y295 S280 + Y295 G258 + Q299 Y267 + Y295 W284 + H321N260 + H321 K269 + Q299 S280 + S304 G258 + S304 Y267 + S304 W284 + S323N260 + S323 K269 + S304 S280 + V326 G258 + R320 Y267 + V326 W284 + H324N260 + H324 K269 + R320 T285 + Y295 G258 + H321 A288 + F289 W284 + V326N260 + V326 K269 + H321 T285 + S304 G258 + S323 A288 + V291 W284 + F328N260 + F328 K269 + S323 T285 + V326 G258 + H324 A288 + Y295 W284 + T334N260 + T334 K269 + H324 M286 + Y295 G258 + V326 A288 + Q299 W284 + D337N260 + D337 K269 + V326 M286 + S304 G258 + F328 A288 + S304 W284 + Q345N260 + Q345 K269 + F328 M286 + V326 G258 + T334 A288 + R320 W284 + G346N260 + G346 K269 + T334 F289 + Y295 G258 + D337 A288 + H321 W284 + G348N260 + G348 K269 + D337 F289 + S304 G258 + Q345 A288 + S323 W284 + T355N260 + T355 K269 + Q345 F289 + V326 G258 + G346 A288 + H324 W284 + S376N260 + S376 K269 + G346 V291 + Y295 G258 + G348 A288 + V326 W284 + D377N260 + D377 K269 + G348 V291 + S304 G258 + T355 A288 + F328 W284 + D379N260 + D379 K269 + T355 V291 + V326 G258 + S376 A288 + T334 W284 + Y382N260 + Y382 K269 + S376 Y295 + Q299 G258 + D377 A288 + D337 W284 + S383N260 + S383 K269 + D377 Y295 + S304 G258 + D379 A288 + Q345 W284 + Q385N260 + Q385 K269 + D379 Y295 + R320 G258 + Y382 A288 + G346 W284 + K391N260 + K391 K269 + Y382 Y295 + H321 G258 + S383 A288 + G348 W284 + K393N260 + K393 K269 + S383 Y295 + S323 G258 + Q385 A288 + T355 W284 + Q395N260 + Q395 K269 + Q385 Y295 + H324 G258 + K391 A288 + S376 W284 + A420N260 + A420 K269 + K391 Y295 + V326 G258 + K393 A288 + D377 W284 + G423N260 + G423 K269 + K393 Y295 + F328 G258 + Q395 A288 + D379 W284 + T444N260 + T444 K269 + Q395 Y295 + T334 G258 + A420 A288 + Y382 W284 + A445N260 + A445 K269 + A420 Y295 + D337 G258 + G423 A288 + S383 W284 + Q449N260 + Q449 K269 + G423 Y295 + Q345 G258 + T444 A288 + Q385 W284 + T459N260 + T459 K269 + T444 Y295 + G346 G258 + A445 A288 + K391 W284 + P473N260 + P473 K269 + A445 Y295 + G348 G258 + Q449 A288 + K393 W284 + C474N260 + C474 K269 + Q449 Y295 + T355 G258 + T459 A288 + Q395 W284 + G476N260 + G476 K269 + T459 Y295 + S376 G258 + P473 A288 + A420 W284 + G477N260 + G477 K269 + P473 Y295 + D377 G258 + C474 A288 + G423 W284 + K484N260 + K484 K269 + C474 Y295 + D379 G258 + G476 A288 + T444 S304 + V326S304 + K393 K269 + G476 Y295 + Y382 G258 + G477 A288 + A445 S304 + Y295S304 + Q395 K269 + G477 Y295 + S383 G258 + K484 A288 + Q449 S304 + S304S304 + A420 K269 + K484 Y295 + Q385 Q299 + S304 A288 + T459 S304 + V326S304 + G423 S304 + T355 Y295 + K391 Q299 + V326 A288 + P473 S304 + Q299S304 + T444 S304 + S376 Y295 + K393 R320 + V326 A288 + C474 S304 + S304S304 + A445 S304 + D377 Y295 + Q395 H321 + V326 A288 + G476 S304 + R320S304 + Q449 S304 + D379 Y295 + A420 S323 + V326 A288 + G477 S304 + H321S304 + T459 S304 + Y382 Y295 + G423 H324 + V326 A288 + K484 S304 + S323S304 + P473 S304 + S383 Y295 + T444 Y295 + P473 S304 + Q345 S304 + H324S304 + C474 S304 + Q385 Y295 + A445 Y295 + C474 S304 + G346 S304 + V326S304 + G476 S304 + K391 Y295 + Q449 Y295 + G476 S304 + G348 S304 + F328S304 + G477 S304 + D337 Y295 + T459 Y295 + G477 Y295 + K484 S304 + T334S304 + K484wherein numbering is according to SEQ ID NO; 13; or

H1 + A37 N54 + F113 K72 + G109 R116 + A174 T165 + A174 N195 + V206 H1 +T40 N54 + R116 K72 + F113 R116 + G184 T165 + G184 N195 + L228 H1 + N54N54 + N125 K72 + R116 R116 + N195 T165 + N195 N195 + G255 H1 + V56 N54 +F133 K72 + N125 R116 + G196 T165 + G196 N195 + A265 H1 + A60 N54 + T134K72 + F133 R116 + A204 T165 + A204 N195 + S280 H1 + K72 N54 + T165 K72 +T134 R116 + V206 T165 + V206 N195 + S304 H1 + G109 N54 + Q172 K72 + T165R116 + L228 T165 + L228 N195 + R320 H1 + F113 N54 + L173 K72 + Q172R116 + G255 T165 + G255 N195 + H321 H1 + R116 N54 + A174 K72 + L173R116 + A265 T165 + A265 N195 + S323 H1 + N125 N54 + G184 K72 + A174R116 + S280 T165 + S280 N195 + K391 H1 + F133 N54 + N195 K72 + G184R116 + S304 T165 + S304 G196 + A204 H1 + T134 N54 + G196 K72 + N195R116 + R320 T165 + R320 G196 + V206 H1 + T165 N54 + A204 K72 + G196R116 + H321 T165 + H321 G196 + L228 H1 + Q172 N54 + V206 K72 + A204R116 + S323 T165 + S323 G196 + G255 H1 + L173 N54 + L228 K72 + V206R116 + K391 T165 + K391 G196 + A265 H1 + A174 N54 + G255 K72 + L228N125 + F133 Q172 + L173 G196 + S280 H1 + G184 N54 + A265 K72 + G255N125 + T134 Q172 + A174 G196 + S304 H1 + N195 N54 + S280 K72 + A265N125 + T165 Q172 + G184 G196 + R320 H1 + G196 N54 + S304 K72 + S280N125 + Q172 Q172 + N195 G196 + H321 H1 + A204 N54 + R320 K72 + S304N125 + L173 Q172 + G196 G196 + S323 H1 + V206 N54 + H321 K72 + R320N125 + A174 Q172 + A204 G196 + K391 H1 + L228 N54 + S323 K72 + H321N125 + G184 Q172 + V206 A204 + V206 H1 + G255 N54 + K391 K72 + S323N125 + N195 Q172 + L228 A204 + L228 H1 + A265 V56 + A60 K72 + K391N125 + G196 Q172 + G255 A204 + G255 H1 + S280 V56 + K72 G109 + F113N125 + A204 Q172 + A265 A204 + A265 H1 + S304 V56 + G109 G109 + R116N125 + V206 Q172 + S280 A204 + S280 H1 + R320 V56 + F113 G109 + N125N125 + L228 Q172 + S304 A204 + S304 H1 + H321 V56 + R116 G109 + F133N125 + G255 Q172 + R320 A204 + R320 H1 + S323 V56 + N125 G109 + T134N125 + A265 Q172 + H321 A204 + H321 H1 + K391 V56 + F133 G109 + T165N125 + S280 Q172 + S323 A204 + S323 A37 + T40 V56 + T134 G109 + Q172N125 + S304 Q172 + K391 A204 + K391 A37 + N54 V56 + T165 G109 + L173N125 + R320 L173 + A174 V206 + L228 A37 + V56 V56 + Q172 G109 + A174N125 + H321 L173 + G184 V206 + G255 A37 + A60 V56 + L173 G109 + G184N125 + S323 L173 + N195 V206 + A265 A37 + K72 V56 + A174 G109 + N195N125 + K391 L173 + G196 V206 + S280 A37 + G109 V56 + G184 G109 + G196F133 + T134 L173 + A204 V206 + S304 A37 + F113 V56 + N195 G109 + A204F133 + T165 L173 + V206 V206 + R320 A37 + R116 V56 + G196 G109 + V206F133 + Q172 L173 + L228 V206 + H321 A37 + N125 V56 + A204 G109 + L228F133 + L173 L173 + G255 V206 + S323 A37 + F133 V56 + V206 G109 + G255F133 + A174 L173 + A265 V206 + K391 A37 + T134 V56 + L228 G109 + A265F133 + G184 L173 + S280 L228 + G255 A37 + T165 V56 + G255 G109 + S280F133 + N195 L173 + S304 L228 + A265 A37 + Q172 V56 + A265 G109 + S304F133 + G196 L173 + R320 L228 + S280 A37 + L173 V56 + S280 G109 + R320F133 + A204 L173 + H321 L228 + S304 A37 + A174 V56 + S304 G109 + H321F133 + V206 L173 + S323 L228 + R320 A37 + G184 V56 + R320 G109 + S323F133 + L228 L173 + K391 L228 + H321 A37 + N195 V56 + H321 G109 + K391F133 + G255 A174 + G184 L228 + S323 A37 + G196 V56 + S323 F113 + R116F133 + A265 A174 + N195 L228 + K391 A37 + A204 V56 + K391 F113 + N125F133 + S280 A174 + G196 G255 + A265 A37 + V206 A60 + K72 F113 + F133F133 + S304 A174 + A204 G255 + S280 A37 + L228 A60 + G109 F113 + T134F133 + R320 A174 + V206 G255 + S304 A37 + G255 A60 + F113 F113 + T165F133 + H321 A174 + L228 G255 + R320 A37 + A265 A60 + R116 F113 + Q172F133 + S323 A174 + G255 G255 + H321 A37 + S280 A60 + N125 F113 + L173F133 + K391 A174 + A265 G255 + S323 A37 + S304 A60 + F133 F113 + A174T134 + T165 A174 + S280 G255 + K391 A37 + R320 A60 + T134 F113 + G184T134 + Q172 A174 + S304 A265 + S280 A37 + H321 A60 + T165 F113 + N195T134 + L173 A174 + R320 A265 + S304 A37 + S323 A60 + Q172 F113 + G196T134 + A174 A174 + H321 A265 + R320 A37 + K391 A60 + L173 F113 + A204T134 + G184 A174 + S323 A265 + H321 T40 + N54 A60 + A174 F113 + V206T134 + N195 A174 + K391 A265 + S323 T40 + V56 A60 + G184 F113 + L228T134 + G196 G184 + N195 A265 + K391 T40 + A60 A60 + N195 F113 + G255T134 + A204 G184 + G196 S280 + S304 T40 + K72 A60 + G196 F113 + A265T134 + V206 G184 + A204 S280 + R320 T40 + G109 A60 + A204 F113 + S280T134 + L228 G184 + V206 S280 + H321 T40 + F113 A60 + V206 F113 + S304T134 + G255 G184 + L228 S280 + S323 T40 + R116 A60 + L228 F113 + R320T134 + A265 G184 + G255 S280 + K391 T40 + N125 A60 + G255 F113 + H321T134 + S280 G184 + A265 S304 + R320 T40 + F133 A60 + A265 F113 + S323T134 + S304 G184 + S280 S304 + H321 T40 + T134 A60 + S280 F113 + K391T134 + R320 G184 + S304 S304 + S323 T40 + T165 A60 + S304 R116 + N125T134 + H321 G184 + R320 S304 + K391 T40 + Q172 A60 + R320 R116 + F133T134 + S323 G184 + H321 R320 + H321 T40 + L173 A60 + H321 R116 + T134T134 + K391 G184 + S323 R320 + S323 T40 + A174 A60 + S323 R116 + T165T165 + Q172 G184 + K391 R320 + K391 T40 + G184 A60 + K391 R116 + Q172T165 + L173 N195 + G196 H321 + S323 T40 + N195 T40 + S323 R116 + L173H1 + Q169 N195 + A204 H321 + K391 T40 + G196 T40 + K391 T40 + A265 H1 +A186 S244 + G255 S323 + K391 T40 + A204 N54 + V56 T40 + S280 H1 + E190S244 + G258 A265 + K269 T40 + V206 N54 + A60 T40 + S304 H1 + A225 S244 +N260 A265 + W284 T40 + L228 N54 + K72 T40 + R320 H1 + K242 S244 + A265A265 + Y295 T40 + G255 N54 + G109 T40 + H321 H1 + S244 S244 + K269A265 + S304 T40 + Q169 R116 + Q169 A204 + A225 H1 + G258 S244 + S280A265 + V326 T40 + A186 R116 + A186 A204 + K242 H1 + N260 S244 + W284K269 + S280 T40 + E190 R116 + E190 A204 + S244 H1 + K269 S244 + Y295K269 + W284 T40 + A225 R116 + A225 A204 + G258 H1 + W284 S244 + S304K269 + Y295 T40 + K242 R116 + K242 A204 + N260 H1 + Y295 S244 + R320K269 + S304 T40 + S244 R116 + S244 A204 + K269 H1 + S304 S244 + H321K269 + R320 T40 + G258 R116 + G258 A204 + W284 H1 + V326 S244 + S323K269 + H321 T40 + N260 R116 + N260 A204 + Y295 A37 + Q169 S244 + V326K269 + S323 T40 + K269 R116 + K269 A204 + S304 A37 + A186 S244 + K391K269 + V326 T40 + W284 R116 + W284 V206 + A225 A37 + E190 S244 + I405K269 + K391 T40 + Y295 R116 + Y295 V206 + K242 A37 + A225 S244 + A421K269 + I405 T40 + S304 R116 + S304 V206 + S244 A37 + K242 S244 + A422K269 + A421 T40 + V326 N125 + Q169 V206 + G258 A37 + S244 S244 + A428K269 + A422 N54 + Q169 N125 + A186 V206 + N260 A37 + G258 S244 + G448K269 + A428 N54 + A186 N125 + E190 V206 + K269 A37 + N260 S244 + D476K269 + G448 N54 + E190 N125 + A225 V206 + W284 A37 + K269 S244 + G477K269 + D476 N54 + A225 N125 + K242 V206 + Y295 A37 + W284 G255 + G258K269 + G477 N54 + K242 N125 + S244 V206 + S304 A37 + Y295 G255 + N260S280 + W284 N54 + S244 N125 + G258 V206 + V326 A37 + S304 G255 + K269S280 + Y295 N54 + G258 N125 + N260 A225 + L228 A37 + V326 G255 + W284S280 + S304 N54 + N260 N125 + K269 A225 + K242 Q172 + A186 G255 + Y295S280 + V326 N54 + K269 N125 + W284 A225 + S244 Q172 + E190 G255 + S304W284 + Y295 N54 + W284 N125 + Y295 A225 + G255 Q172 + A225 G255 + V326W284 + S304 N54 + Y295 N125 + S304 A225 + G258 Q172 + K242 G258 + N260W284 + R320 N54 + S304 F133 + Q169 A225 + N260 Q172 + S244 G258 + A265W284 + H321 N54 + V326 F133 + A186 A225 + A265 Q172 + G258 G258 + K269W284 + S323 V56 + Q169 F133 + E190 A225 + K269 Q172 + N260 G258 + S280W284 + V326 V56 + A186 F133 + A225 A225 + S280 Q172 + K269 G258 + W284W284 + K391 V56 + E190 F133 + K242 A225 + W284 Q172 + W284 G258 + Y295W284 + I405 V56 + A225 F133 + S244 A225 + Y295 Q172 + Y295 G258 + S304W284 + A421 V56 + K242 F133 + G258 A225 + S304 Q172 + S304 G258 + R320W284 + A422 V56 + S244 F133 + N260 A225 + R320 L173 + A186 G258 + H321W284 + A428 V56 + G258 F133 + K269 A225 + H321 L173 + E190 G258 + S323W284 + G448 V56 + N260 F133 + W284 A225 + S323 L173 + A225 G258 + V326W284 + D476 V56 + K269 F133 + Y295 A225 + V326 L173 + K242 G258 + K391W284 + G477 V56 + W284 F133 + S304 A225 + K391 L173 + S244 G258 + I405Y295 + S304 V56 + Y295 T134 + Q169 A225 + I405 L173 + G258 G258 + A421Y295 + R320 V56 + S304 T134 + A186 A225 + A421 L173 + N260 G258 + A422Y295 + H321 V56 + V326 T134 + E190 A225 + A422 L173 + K269 G258 + A428Y295 + S323 A60 + Q169 T134 + A225 A225 + A428 L173 + W284 G258 + G448Y295 + V326 A60 + A186 T134 + K242 A225 + G448 L173 + Y295 G258 + D476Y295 + K391 A60 + E190 T134 + S244 A225 + D476 L173 + S304 G258 + G477Y295 + I405 A60 + A225 T134 + G258 A225 + G477 A174 + A186 N260 + A265Y295 + A421 A60 + K242 T134 + N260 L228 + K242 A174 + E190 N260 + K269Y295 + A422 A60 + S244 T134 + K269 L228 + S244 A174 + A225 N260 + S280Y295 + A428 A60 + G258 T134 + W284 L228 + G258 A174 + K242 N260 + W284Y295 + G448 A60 + N260 T134 + Y295 L228 + N260 A174 + S244 N260 + Y295Y295 + D476 A60 + K269 T134 + S304 L228 + K269 A174 + G258 N260 + S304Y295 + G477 A60 + W284 T134 + V326 L228 + W284 A174 + N260 N260 + R320S304 + R320 A60 + Y295 T165 + Q169 L228 + Y295 A174 + K269 N260 + H321S304 + H321 A60 + S304 T165 + A186 L228 + S304 A174 + W284 N260 + S323S304 + S323 A60 + V326 T165 + E190 L228 + V326 A174 + Y295 N260 + V326S304 + V326 K72 + Q169 T165 + N195 K242 + S244 A174 + S304 N260 + K391S304 + K391 K72 + A186 T165 + A225 K242 + G255 G184 + A186 N260 + I405S304 + I405 K72 + E190 T165 + K242 K242 + G258 G184 + E190 N260 + A421S304 + A421 K72 + A225 T165 + S244 K242 + N260 G184 + A225 N260 + A422S304 + A422 K72 + K242 T165 + G258 K242 + A265 G184 + K242 N260 + A428S304 + A428 K72 + S244 T165 + N260 K242 + K269 G184 + S244 N260 + G448S304 + G448 K72 + G258 T165 + K269 K242 + S280 G184 + G258 N260 + D476S304 + D476 K72 + N260 T165 + W284 K242 + W284 G184 + N260 N260 + G477S304 + G477 K72 + K269 T165 + Y295 K242 + Y295 G184 + K269 N195 + A225R320 + H321 K72 + W284 T165 + S304 K242 + S304 G184 + W284 N195 + K242R320 + V326 K72 + Y295 Q169 + Q172 K242 + R320 G184 + Y295 N195 + S244H321 + V326 K72 + S304 Q169 + L173 K242 + H321 G184 + S304 N195 + G258S323 + V326 G109 + Q169 Q169 + A174 K242 + S323 A186 + E190 N195 + N260V326 + K391 G109 + A186 Q169 + G184 K242 + V326 A186 + N195 N195 + K269V326 + I405 G109 + E190 Q169 + A186 K242 + K391 A186 + G196 N195 + W284V326 + A421 G109 + A225 Q169 + E190 K242 + I405 A186 + A204 N195 + Y295V326 + A422 G109 + K242 Q169 + N195 K242 + A421 A186 + V206 N195 + S304V326 + A428 G109 + S244 Q169 + G196 K242 + A422 A186 + A225 N195 + V326V326 + G448 G109 + G258 Q169 + A204 K242 + A428 A186 + L228 G196 + A225V326 + D476 G109 + N260 Q169 + V206 K242 + G448 A186 + K242 G196 + K242V326 + G477 G109 + K269 Q169 + A225 K242 + D476 A186 + S244 G196 + S244E190 + Y295 G109 + W284 Q169 + L228 K242 + G477 A186 + G255 G196 + G258E190 + S304 G109 + Y295 Q169 + K242 E190 + A204 A186 + G258 G196 + N260E190 + R320 G109 + S304 Q169 + S244 E190 + V206 A186 + N260 G196 + K269E190 + H321 G109 + V326 Q169 + G255 E190 + A225 A186 + A265 G196 + W284E190 + S323 F113 + Q169 Q169 + G258 E190 + L228 A186 + K269 G196 + Y295E190 + V326 F113 + A186 Q169 + N260 E190 + K242 A186 + S280 G196 + S304E190 + K391 F113 + E190 Q169 + A265 E190 + S244 A186 + W284 G196 + V326E190 + I405 F113 + A225 Q169 + K269 E190 + G255 A186 + Y295 A186 + G448E190 + A421 F113 + K242 Q169 + S280 E190 + G258 A186 + S304 A186 + D476E190 + A422 F113 + S244 Q169 + W284 E190 + N260 A186 + R320 A186 + G477E190 + A428 F113 + G258 Q169 + Y295 E190 + A265 A186 + H321 E190 + N195E190 + G448 F113 + N260 Q169 + S304 E190 + K269 A186 + S323 E190 + G196E190 + D476 F113 + K269 Q169 + R320 E190 + S280 A186 + V326 Q169 + A422E190 + G477 F113 + W284 Q169 + H321 E190 + W284 A186 + K391 Q169 + A428A186 + A422 F113 + Y295 Q169 + S323 Q169 + I405 A186 + I405 Q169 + G448A186 + A428 F113 + S304 Q169 + V326 Q169 + A421 A186 + A421 Q169 + D476F113 + V326 Q169 + K391 Q169 + G477wherein numbering is according to SEQ ID NO: 14.

Stability of a parent polypeptide may be improved by introducing apairwise deletion within the B domain of parent polypeptide. Thus, inone embodiment, the said variant comprises

-   -   a) a deletion and/or a substitution at two or more positions        corresponding to positions R181, G182, D183, and G184 of the        amino acid sequence as set forth in SEQ ID NOs: 7 or 10, and    -   b) an alteration at one or more positions corresponding to        positions H1, T5, G7, Q11, N16, V17, Q32, A37, T40, P45, W48,        G50. T51, N54, V56, K72. R87, Q98, M105, G109, F113, R116, Q118,        Q125, G133, T134, W140, G142, G149, T165, W167, Q169, R171,        Q172, L173, A174, G184, A186, E190, T193, N195, A204, V206,        P211, I214, V215, L217, L219, A225, L235, V238, K242, S244,        M246, M248, L250, G255, Q256, N260, A263, V264, Y267, K269,        N270, G273, S280, W284, T285, M286, F289, V291, Y295, Q299,        R320, H321, S323, H324, V326, F328. T334, D337, Q345, G346,        G348, T355, S376. D377, D379, Y382, S383, Q385, K391, K393,        Q395, A420, G423, T444, A445, Q449, T459, P473, C474, G476,        G477, and K484 of SEQ ID NO: 13; or H1, A37, T40, N54, V56, A60,        K72, G109, F113, R116, N125, F133, T134, T165, Q172, L173, A174,        G184, N195, G196, A204, V206, L228, G255, A265, S280, S304,        R320, H321, S323, K391, I405, A421, A422, A428, R439, G448,        W467, D476, and G477 of SEQ ID NO: 14.

The term “pairwise deletion” as used herein, refers to a deletion of anamino acid in two positions. Said two positions may be adjacent to oneanother but may also be separated by one, two, three, four, or fiveamino acids.

In a particular embodiment, the deletion a) is selected from the groupconsting of R18I+G182, R18I+D183, R18I+G184, G182+D183, G182+G184, orD18S+G184.

In an embodiment, variant comprises one or more of the followingalterations; H1*, T5K, G7K, G7A, Q11H, N16S, N16H, V17L, Q32S, A37H,A37M, A37V, A37S, A37Y, A37R, A37L, T40G, T40K, P45A, W48G, W48Y, W48F,G50A, T51K, T51E, T51G, T51A, T51S, T51G, T51D. N54S, V56T, K72R, K72H,K72S, K72Q, K72E, K72N, K72A, K72M, R87S, Q98S, Q98A, M105F, M105I,M105V, M105L, G109A, G109S, F113W, F113S, F113N, F113Y, F113R, F113L,F113Q, R116Q, R116V, R116K, R116W, R116L, R116A, R116H, R116M, R116E,R116S, R116I, R116G, Q118N, Q118K, Q118G, Q118S, Q118F, Q118R, Q125P,Q125K, Q125A, Q125T, G133S, T134E, W140Y, G142T, G149Q, T165S, T165G,T165V, W167I, W167G, W167F, W167R, W167S, W167H, W167L, W167M, W167Y,Q169E, R171H, Q172G, Q172R, Q172N, Q172D, Q172Y, Q172M, Q172S, Q172T,Q172K, Q172H, Q172E, L173V, L173G, L173H, L173A, L173I, L173P, L173I,L173F, L173M, A174S, A174D, A174P, A174M, A174T, A174H, A174K, A174G,A174Q, A174N, A174V, A174L, G184T, A186D, A186N, A186E, A186Q, A186H,E190P, T193K, N195F, A204T, A204V, A204G, A204G, V206L, V206S, V206Y,P211D, I214G, I214H. I214S, I214T, I214L, I214E, I214W, V215T, L217T,L217Q, L219V, L219H, A225V, L235V, L235A, V238A, V238I, V238G, K242Q,S244Q, M246L, M246A, M246I, M246F, M246V, M246S, M248T, L250I, L250V,L250I, L250A, L250F, L250M, G255N, G255A, G255S, Q256A, N260G, A263G,V264I, V264T, Y267I, Y267M, Y267H, Y267L, K269Q, N270G, N270T, G273R,S280W, S280L, S280T, S280A, S280K, S280Q, W284H, T285L, T285Q, M286F,M286L, A288L, A288V, F289I, F289L. V291G, V291A, V291T, Y295F, Y295N.Q299V. S304R, S304N, R320A, R320V, H321Y, S323N, H324L, V326L, F328L,F328M, F328V, F328I, T334S, D337H, Q345D, G346T, G346D, G346P, G348S,G348P, T355L, T355F, S376H, S376T, S376V, D377H, D377S, D377A, D377Q,D379S, D379G, D379R, D379A, Y382M, Y382I, Y382L, Y382F, S383G, S383A,Q385L, K391A, K391Y, K391V, K391M, K391E, K391D, K391R, K391H, K391W,K391I, K391Q, K391L, K393Y, K393R, K393Q, K393S, Q395P, T400P, H402R,A420Q, A420S, A420K, A420L, G423H, T444Q, T444S, T444D, T444Y, T444H,T444V, T444R, T444A, A445Q, Q449T, T459N, P473R, P473A, P473G, P473T,P473K, Q474V, G476K, G477A, G477Q, K484A, K484G, K484P, K484E, K484Q,and K484S of SEQ ID NO: 13; or H1*, G7A, A37H, T40D, W148Y, W48F, N54S,V56T, A60V, K72R, Q98A, G109A, F113Q, R116H, R116V, R116Q, N125D, F133Q,T134E, T165G, Q169E, Q172D, Q172G, Q172N, L173V, A174S, G184T, A186D,A186N, A186E, A186Q, A186H, E190P, N195F, G196R, A204G, V206L, V206Y,A225V, L228I, K242Q, S244Q, G255A, G255S, N260G, A265G, K269Q, N270T,S280Q, W284H, A288L, A288V, F289L, Y295F, Y295N, S304N, S304R, S304N,R320A, H321Y, S323N, V326L, K391A, I405L, A421H, A422P, A428T, G448D,D476K, D476G, D476N, D476Y, G477S, G477A, G477T, and G477Q of SEQ ID NO:14.

In a particular embodiment, the variant has an IF of >1 when compared tosaid parent polypeptide, and wherein said variant is selected from

-   G182*+D183*+N195F-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+R87S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+T40G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+T51K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72H+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37H+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37M+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37V+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37R+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+F113W+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+F113S+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+F113N+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+F113Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+F113R+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+Q118N+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+R116K+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+R116W+A174S+G182A+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1A+N54S+V56T+G109A+G142T+A174S+G182A+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+Q125P+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+Q125K+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381G+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246T+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+V213I+K391A+G476K-   H1*+A37L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+Q118K+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1A+N54S+V56T+G109A+Q125A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377G+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+D377R+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214G+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381A+K391A+G476K-   H1*+N54S+V56T+G109A+W167I+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1A+N54S+V56T+G109A+W167G+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346S+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+G346P+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L-H214H+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214S+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+I214T+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420Q+G476K-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420S+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420K+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420L+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Y+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391R+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K391A+P473R+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473T+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444S+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444D+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Y+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280W+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280I+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280A+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255N+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285Q+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q449T+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473K+G476K-   H1*+N54S+V56T+K72S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+T40K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K-   H1*+G50A+N54S+V5    G109A++Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484A-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484G-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484P-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484E-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484Q-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484S-   H1*K+G50A+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+W140Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+Q98S+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+H324L+K391A+G476K-   H1*+N54S+V56T+G109A+G149Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A-   H1*+N54S+V56T+G109AG255A++A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+G50A+N54S+V56T+G109A+F113L+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+G477Q-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q345D+K391A+G476K+G477Q-   H1*+G50A+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264I+K391A+G423H+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320V+K391A+G476Y-   H1*+T5K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+R116M+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+Q172Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217V+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217H+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P211D+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Q+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444H+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444V+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444R+G476K-   H1*+G50A+N54S+V56I+G109A+L173V+A174S+G182*+D183*+N195F+A204V+V206L+K391A+G476K-   H1*+G50A+N54S+V56T+G109A+F113L+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K-   H1*+N54S+V56T+G109A+Q118G+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280K+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A-   H1*+N54S+V56T+G109A+Q118S+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G337H+Q385L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382M+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K-   H1*+N54S+V56T+K72R+M105F+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K-   H1*+N54S+V56T+M105F+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+M105F+G109A+Q118F+T143E+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+D377H+K391A+G476K-   H1*+T51E+N54S+V56T+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+L173A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q299V+K391A+G476K-   H1*+N54S+V56T+G109A+L173G+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T355L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T355F+K391A+G476K-   H1*+G50A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K-   H1*+G50A+N54S+V56T+G109A+A174E+G182*+D183*+N195F+A204T+V206L+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K-   H1*+N54S+V56T+M105I+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246L+K391A+G476K-   H1*+T51G+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+T51A+N54S+V56T+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+T51 S+N54S+V56T+G109A+A174P+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+T51G+N54S+V56T+G109A+A174M+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72A+G109A+W167S+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+W167R+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72Q+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K-   H1*+Q11H+N54S+V56T+G109A+Q118R+T134E+A174S+G184T+G182*+D183*+N195F+V206L+D377H+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K-   H1*+N54S+V56T+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+G184I+N195F+V206L+D377H+K391A+G476K-   H1*+N54S+V56T+G109A+Q172D+A174Q+G182*+D183*+N195F+V206L+K391A+G476K+G477A-   H1*+N54S+V56T+K72A+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+W167S+G182*+D183*+N195F+A174S+V206L+K391A+G476K-   H1*+N54S+V56T+K72H+G109A+W167S+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T    K72R+G109A+W167T+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72E+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   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H1*+A37H+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+F113Q+67F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+T459N+G476K-   H1*+N54S+V56T+G109A+F113Q+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K-   H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+A60V+G109A+R116H+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37V+N54S+V56T+A60V+G109A+R6Q+I165G+A174S+G182*+D183*+N195F+V206+K391A+G476K-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206+K391A+G476K-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   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H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+G476K-   H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+G273R+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L-   H1*W48G+G109A+G182*+D183*+N195F+V206L+K391A+G476K-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A-   H1*+N54S+V56T+G109A+F113Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+P473R+G476K-   H1*+N54S+V56T+K72R+G109A+R116Q+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K-   H1*+A37V+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37V+N54S+V56I+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K-   H1*+V56A+G109A+A174S+G182*+D183*+N195F+V206L+G476K-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+G476K-   G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391T+G476K-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+G476K-   H1*+N54S+V56T+G109S+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K-   H1*+N54S+V56T+G109A+F113Q+67F+Q172N+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K-   H1*+N54S+V56T+G109A+R116H+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K-   H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37H+N54S+V56T+G109A+R6H+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K-   H1*+G109A+G182*+D183*+N195F+V206L+K391A+G476K-   G109A+G182*+D183K+N195F+V206L+G476K-   H1*+G109A+G182*+D183*+N195F+K391A-   H1*+N54S+V56T+G109A+G133S+A174S+G182*+D183*+N195F+K391A+G476H-   H1*+N54S+V56T+G109A+R116A+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+A37V+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+P45A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K-   H1A+N54S+V56T+G109A+P124A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P364A+K391A+C474V+G476K-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K-   H1*+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+V264F+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382L+K391A+G476K-   H1A+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+Q256A+K391A+G476K-   H1*+N54S+V56T+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+T165V+A174S+G182*+D183A+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1A+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382F+K391A+G476K-   H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q385L+K391A+G476K-   H1*+N54S+V56T+R87S+G109A+R171H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172G+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116W+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+A186N+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A288V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+G184I+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270T+K391A+G476K,-   H1A+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174K+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A225V+K391A+G476K,-   H1*+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255S+K391A+G476K.-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+Q169E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+W284H+K391A+G476K,-   H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+S304R+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182+D183*+G184I+N195F+V206L+K391A+P473R,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174K+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183K+N195F+V206L+Y295F+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G476K,-   F113Q+R116H+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A288L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   Q169E+Q172K+A174*+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   F113Q+R116Q+D183*+G182*+N195F,-   N54S+V56T+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   Q169E+Q172K+G182*+D183*+N195F,-   G182*+D183*+A186D,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,-   G182*+D183*+A186N,-   H1*+N54S+V56T+G109A+A174S+V206L+G182*+D183*+K391A+G476K,-   H1*+N54S+V56T+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F289L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S244Q+K391A+G476K,-   G182*+D183*+F328L,-   G182*+D183*+N195F+A288V,-   G182*+D183*+A186N+N195F,-   G182*+D183*+E190P+N195F,-   W140Y+G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A225V+K391A+G476K,-   G182*+D183*+A186D+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+W48Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F+V238A,-   G182*+D183*+Y295N,-   Q172G+G182*+D183*,-   F113Q+G182*+D183*+N195F,-   H1*+N54S+V56T+Q98A+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F+Y295F,-   G182*+D183*+A186E,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206Y+K391A+G476K,-   G182*+D183*+N195F+\A/284H,-   G182*+D183*+A186Q+N195F,-   K72R+G182*+D183*,-   D183*+G182*+N195F+V326L,-   D183*+G182*+A186E+N195F,-   Q169E+G182*+D183*+N195F,-   D183*+G182*+N195F+K242Q,-   G7A+G182*+D183*+N195F,-   D183*+G182*+N195F+N260G,-   D183*+G182*+R321A+S323N,-   D183*+G182*+W284H,-   H1*+D183*+G182*,-   D183*+G182*+A186H+N195F,-   D183*+G182*+F289V,-   D183*+G182*+K391A,-   D183*+G182*+S304R,-   W167F+G182*+D183*+N195F,-   F113Q+R116H+D183*+G182*,-   D183*+G182*+N270G,-   D183*+G182*+S244Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   D183*+G182*+N195F+Y295N,-   W48F+D183*+G182*,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   D183*+G182*I-A186Q,-   W140Y+D183*+G182*,-   D183*+G182*+K242Q,-   D183*+G182*+N206L,-   D183*+G182*+N195F+V206F,-   Q169E+D183*+G182*,-   D183*+G182*+N195F+R320A,-   G182*I-D183*+G184T+N195F,-   D183*+G182*+G184T,-   N54S+V56T+D183*1-G182*,-   D183*+G182*+P473R,-   W48Y+D183*+G182*,-   D183*+G182*+R323A,-   G7A+D183*+G182*,-   G109A+D183+G182*,-   W167F+D183*+G182*,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   A174S+D183*4-G182*,-   R116Q+D183*+G182*,-   D183*+G182*+N195+V291A,-   Q172K+D183*+G182*,-   N54S+D183*+G182*,-   D183*+G182*+N195F+S323N,-   D183*+G182*+N195F+M246V,-   W48Y+D183*+G182*+N195F,-   D183*+G182*+N195F+S304R,    -   V56T+D183*+G182*, wherein numbering is according to SEQ ID NO;        13; and-   N54S+G182*+D183*+N195F,-   G109A+G182*+D183*+N195F,-   G182*+D183*+N195F+K391A,-   G182*+D183*+N195F+G476K,-   H1*+G182*+D183*+N195F,-   N54S+G182*+D183*+N195F,-   V56T+G182*+D183*A-N195F,-   G182*+D183*+N195F+I405L,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T+D476K,-   A174S+G182*+D183*+N195F,-   H1*+N54S+V56I+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476G,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477S,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S304N+I405L+A421H+A422P+A428T+D476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476G+G477T,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477Q.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476N,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476Y,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206I+I405L+A421H+A422P+A428I-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+A204G+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+G196R+V206L+G255A+I405L+A421H+A422P+A428T+N475S,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+T40D+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+N125D+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116Q+G133Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T+G448D,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+I173V+A174S+G182*+D1*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+F116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+M105F+G182*+D183*+N195F+V206L+L228I+R320A+S323N+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+V120L+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,    wherein numbering is according to SEQ ID NO:14.

As can be seen from the data obtained in Examples 3 and 4, all testedvariants have an Improvement Factor (IF) of at least 1.0, i.e. at leaston par with a parent polypeptide having SEQ ID NO: 15, when tested ineither (i) a detergent Model A at 15° C. and an enzyme concentration of0.05 mg/L, (ii) a detergent Model A at 15° C. and an enzymeconcentration of 0.2 mg/L, (iii) a detergent Model J at 15° C. and anenzyme concentration of 0.05 mg/L, or (iv) a detergent Model J at 15° C.and an enzyme concentration of 0.2 mg/L. Thus, the variants of thepresent invention have even in different model detergent compositions,at a low temperature as well as in a low concentrations, a washperformance at least that of the parent polypeptide having SEQ ID NO:15. Specifications of the model detergents and specific test conditionsfor the AMSA, can be seen in Examples 3 and 4.

In another embodiment, the variant is selected from the group consistingof;

-   G182*+D183*+N195F+V206F+N260P+L312I+L313I+R320A+T355L+L389I+T400P,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G50A+T51A+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+T40K+N54S+V56T+G109A+G149H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+Q22N+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+H28N+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N29S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+H28N+N29S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+R176K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+R176K+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+N175G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+Y295N+Q299T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K269S+A274K+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235I+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+V238A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q365S+K391A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+H402R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320S+H321N+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125S+A174S+G182*+D183A+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A265G+K391A+G476K,-   H1*+T51Q+N54S+V56T+G109A+A174S+G182*+D183*4N195F+Y203F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+N175Q+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+H28N+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+M202V+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+Y203G+V206L+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+G110N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125S+A174S+N175G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A265G+V291A+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246F+A265G+V291A+F328L+Q365S+K391A+G476K,-   H1*+N16Y+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+G337E+D377H+K391A+G476K,-   H1*+I9L+N54S+V56T+G109A+Q125S+V131T+A174*+G182*+D183*+V206L+Y267F+F289H+Q361E+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172G+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116W+Q169E+Q172K+A174*+G182    D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+G184I+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+A186N+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A288V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270T+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+C)    172K+A174*+G182*+D183*+N195F+V206L+A225V+K391A+G476K,-   H1*+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+Q169E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+W284H+K391A+G476K,-   H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+S304R+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184I+N195F+V206L+K391A+P473R,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G476K,-   F113Q+R116H+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A288L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   Q169E+Q172K+A174*+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K269Q+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   F113Q+R116Q+D183*+G182*+N195F,-   N54S+V56T+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   Q169E+Q172K+G182*+D183*+N195F,-   G182*+D183*+A186D,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,-   G182*+D183*+A186N,-   H1*+N54S+V56T+G109A+A174S+V206L+G182*+D183*+K391A+G476K,-   H1*+N54S+V56T+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+Q172K+A174*+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F289L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S244Q+K391A+G476K.-   G182*+D183*+F328L,-   G182*+D183*+N195F+A288V,-   G182*+D183*+A186N+N195F,-   G182*+D183*+E190P+N195F,-   W140Y+G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+25V+K391A+G476K,-   G182*+D183*+A186D+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+W48Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F+V238A,-   G182*+D183*+Y295N,-   Q172G+G182K+D183*,-   F113Q+G182*+D183*+N195F,-   H1*+N54S+V56T+C298A+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F+Y295F,-   G182*+D183*+A186E.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206Y+K391A+G476K,-   G182K+D183K+N195F+W284H,-   G182*+D183*+A186Q+N195F.-   K72R+G182*+D183*,-   D183*+G182*A-N195F+V326L,-   D183*+G182*+A186E+N195F,-   Q169E+G182*+D183*+N195F,-   D183*+G182*+N195F+K242Q,-   G7A+G182*+D183K+N195F,-   D183*+G182*+N195F+N260G,-   D183A+G182*+R321A+S323N,-   D183*+G182*+W284H,-   H1*+D183*+G182*,-   D183*+G182*+A186H+N195F,-   D183*+G182*A+289V,-   D183*+G182*+K391A,-   D183*+G182*+S304R,-   W167F+G182*+D183*+N195F.-   F113Q+R116H+D183*+G182*,-   D183*+G182*+N270G.-   D183A+G182*+S244Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   D183*+G182*+N195F+Y295N,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K-   D183*+G182*+A186Q,-   D183*+G182*+N195F+V206F,-   D183*+G182*+N195F+R320A,-   G182*+D183*+G184T+N195F,-   N54S+V56T+D183*+G182*,-   W48Y+D183*+G182*,-   A174S+D183*+G182*,-   G7A+D183*+G182*,-   N54S+D18S+G182*,-   D183*+G182*+N195F+M246V,-   W48Y+D183*+G182*+N195F,-   D183*+G182*+N195F+S304R,    -   wherein numbering is according to SEQ ID NO: 13, and wherein the        IF is determined by use of Model A detergent.

In one embodiment, the IF is determined by use of Model A detergent at atemperature of 15° C. In a particular embodiment, the variants have anIF of >1 as compared to the parent polypeptide, wherein the IF isdetermined by use of Model A detergent at a temperature of 15° C. and aconcentration of 0.05 mg/L. It can be seen from the Tables in theExamples herein disclosed which such variants may be.

In another embodiment, the variant has an IF of at least 1.0 whencompared to the parent polypeptide when tested in Model J detergent, andwherein the variant is selected from the group consisting of:

-   G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T40G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37M+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37R+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+G142T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125P+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+M246T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V213T+K391A+G476K,-   H1*+A37L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377R+K391A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381A+K391A+G476K,-   H1*+N54S+V56T+G109A+W167I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167G+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+G346S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420S+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420K+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420L+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Y+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473T+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182A+D183*+N195F+V206L+K391A+T444S+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444D+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280W+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+S280L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280T+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+G255N+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q449T+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K391A+P473K+G476K,-   H1*+N54S+V56T+K72S+G109A+A174S+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+T40K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A++Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484A.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484G.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484P,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484E.-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K391A+G476K+K484Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484S,-   H1*K+G50A+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+Q98S+G109A+A174S+G182*+D183A+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+H324L+K391A+G476K,-   H1*+N54S+V56T+G109A+G149Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,-   H1*+N54S+V56T+G109A+G255A++A174S+G182K+D183*+N195F+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+F113L+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+G477Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q345D+K391A+G476K+G477Q,-   H1*+G50A+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264I+K391A+G423H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320V+K391A+G476Y,-   H1*+T5K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P211D+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391    Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444R+G476K,-   H1*+G50A+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204V+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+F113L+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280K+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A.-   H1*+N54S+V56T+G109A+Q118S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G337H+Q385L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+Y382M+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*-M54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+M105F+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+T134E+A174S+G182K+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+M105F+G109A+Q118F+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+R320A+S323N+D377H+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+L173A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q299V+K391A+G476K.-   H1A+N54S+V56T+G109A+L173G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T355L+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+M195F+V206L+T355F+K391A+G476K.-   H1*+G50A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+A174E+G182*+D183*+N195F+A204T+V206L+K391A+G476K.-   H1*-M54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+V56T+M105I+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246L+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174D+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+A174P+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+A174M+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D*+N195F+V206L+D377H+K391A+G476K,-   H1*+Q11H+N54S+V56T+G109A+Q118R+T134E+A174S+G184I+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T    K72R+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174Q+G182*+D183*+N195F+V206L+K391A+G476K+G477A,-   H1*+N54S+V56T+K72A+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167S+G182*+D183*+N195F+A174S+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+W167S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72E+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184A+T193K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+V291G+D377H+K391A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+F328L+D377H+K391A+G476K,-   H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+G184I+N195F+V206L+K391A+G47-   6K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+V238A+D377H+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206F328M+D377H+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328V+D377H+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+D377H+K391A+G476K.-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K.-   H1*+N54S+V56I+G109A+L173H+A174S+G182*+D183A+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1A+N16S+N54S+V56T+G109A+A174S+G182A+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72N+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72N+G109A+W167L+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72A+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183K+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*4N195F+G184T+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184I+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*4N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377R+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,-   H1*+N54S+V56T+G109A+R116E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346D+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,-   H1*+N54S+V56T+G109A+R116S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377Q+K391A+G476K,-   H1*+N54S+V56T+G109A+R116I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174F+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51D+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172R+A174S+K179E+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72Q+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72M+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+Q172M+A174S+G182    D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174D+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174K+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+A174G+G182A+D183A+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K391A+K391S+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444A+G476K,-   H1*+N54S+V56T+G109A+F113L+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+A174E+G182*+D183*+N195F+A204T+V206L+S323N+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+A225F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382I+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+I214E+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L-H214W+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+A204T+V206L+D377H+K391A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204S+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T165S+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T334S+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A263G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M286F+D377H+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V26L+Y267I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235A+D377H+K391A+G476K,-   H1*+N54S+V56T+M105L+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+M105I+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1A+N54S+V56T+M105V+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D18S+N195F+V206L+M24    D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391M+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391E+G476K,-   H1*+N54S+V56T+G109A+T165G+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54R+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54L+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174V+G182*+D183*+N195F+V206L+K391A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+D377H+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246S+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174L+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391D+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391H+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391 W+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391I+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250    T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+L250F+D377H+K39A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391Q+G476K,-   H1*+N54S+V56T+G109A+Q172H+L173A+A174P+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56I+G109A+Q172E+L173A+A174R+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+K72Q+G109A+W167R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184I+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173I+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+L173A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267H+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238G+K391A+G476K,-   H1*+N54S+V56T+M105V+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264I+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+K391A+G476K,-   H1*+N54S+V56T+G109A+W167H+Q172N+L173A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172E+L173P+A174K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+L173T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+L173V+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173F+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173T+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+L173V+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173M+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173F+A174P+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+Q172E+L173V+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250M+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204S+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T334S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A263G+M286F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A263G+M286L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267I+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391L+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G12W+D*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+A204G+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182+D183*+N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A265G+K391A+T444Q+G476K+G477A,-   H1*+A37V+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G346T+G477A+G476K,-   H1*+N54S+V56T+G109A+R116Q+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G346T+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109S+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+V264I+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280Q+H321Y+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D15F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+R116H+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+67F+Q172R+A174S+G182*+D183*+N195F+V206L+F289I+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+A265G+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+T165G+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+I67F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51V+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280Q+H321Y+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+G133Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+Q395P+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R6H+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+G184I+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172G+A174S+G182*+N5F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109S+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109S+F113Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184I+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+A445Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+\N167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+G133Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172N+L173V+A74S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+A37H+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+T459N+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+k    167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116H+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+\N167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116A+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L,-   N54S+V56T+G109A+G182*+D183*+N195F,-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+G476K,-   H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+G273R+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L,-   H1*+W48G+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A,-   H1*+N54S+V56T+G109A+F113Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+R116Q+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+T165    G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+V56A+G109A+A174S+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+G476K.-   G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391T+G476K,-   H1A+N54S+V56T+K72R+G109A+F113Q+R116H+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109S+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444    Q+G476K-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1A+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+T444    Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116H+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D*+N195F+V206L+M246F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,-   H1*+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   G109A+G182*+D183*+N195F+V206L+G476K,-   H1*+G109A+G182*+D183*+N195F+K391A,-   H1*+N54S+V56T+G109A+G133S+A174S+G182*+D183*+N195F+K391A+G476H,-   H1*+N54S+V56T+G109A+R116A+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+P45A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K.-   H1*+N54S+V56T+G109A+P124A+A174S+G182*+D183K+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+P364A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1A+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382L+K391A+G476K.-   H1*+G7K+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+Q256A+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T165V+A174S+G182K+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382F+K391A+G476K,-   H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q385L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+R171H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   N54S+G182*+D183*+N195F,-   G109A+G182*+D183*+N195F.-   A174S+G182*+D183K+N195F,-   G182*+D183*+N195F+K391A.-   G182*+D183A+N195F+G476K,-   H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G    A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172G+A174*+G182*+D183*+N195F+V206L+K391A+G476K;-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116W+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+A186N+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A288V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q72K+A174*+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F    V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270T+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A225V+K391A+G476K,-   H1*+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q72K+A174*+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+Q169E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+W284H+K391A+G476K,-   H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+S304R+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+Q169E+Q172K+A174    G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G476K,    F113Q+R116H+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A288L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   Q169E+Q172K+A174W+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   F113Q+R116Q+D183*+G182*+N195F,-   N54S+V56T+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   Q169E+Q172K+G182*+D183*+N195F,-   G182*+D183*+A186D,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,-   G182*+D183*+A186N,-   H1*+N54S+V56T+G109A+A174S+V206L+G182*+D183*+K391A+G476K,-   H1*+N54S+V56T+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F289L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S244Q+K391A+G476K,-   G182*+D183*+F328L,-   G182*+D183*+N195F+A288V,-   G182*+D183*+A186N+N195F,-   G182*+D183*+E190P+N195F,-   W140Y+G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A225V+K391A+G476K,-   G182*+D183*+A186D+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+W48Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F+V238A,-   G182*+D183*+Y295N,-   Q172G+G182*+D183*,-   F113Q+G182*+D183*+N195F,-   H1*+N54S+V56T+Q98A+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F+Y295F,-   G182*+D183*+A186E,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206Y+K391A+G476K,-   G182*+D183*+N195F+W284H,-   G182*+D183*+A186Q+N195F,-   K72R+G182*+D183*,-   D183*+G182*+N195F+V326L,-   D183*+G182*+A186E+N195F,-   Q169E+G182*+D183*+N195F,-   D183*+G182*+N195F+K242Q,-   G7A+G182*+D183*+N195F,-   D183*+G182*+N195F+N260G,-   D183*+G182*+R321A+S323N,-   D183*+G182*+W284H,-   H1*+D183*+G182*,-   D183*+G182*+A186H+N195F,-   D183*+G182*+F289V,-   D183*+G182*+K391A,-   D183*+G182*+S304R,-   W167F+G182*+D183*+N195F,-   F113Q+R116H+D183*+G182*,-   D183*+G182*+N270G,-   D183*+G182*+S244Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   D183*+G182*+N195F+Y295N,-   W48F+D183*+G182*,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   D183*+G182*+A186Q,-   W140Y+D183*+G182*,-   D183*+G182*+K242Q,-   D183*+G182*+V206L,-   D183*+G182*+N195F+V206F,-   Q169E+D183*+G182*,-   D183*+G182*+N195F+R320A,-   G182*+D183*+G184T+N195F,-   D183*+G182*+G184T,-   D183*+G182*+P473R,-   W48Y+D183*+G182*,-   D183*+G182*+R323A,-   G7A+D183*+G182*,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   A174S+D183*+G182*,-   D183*+G182*+N195F+S323N,-   D183*+G182*+N195F+M246V,-   W48Y+D183*+G182*+N195F,-   V56T+D183*+G182*,    wherein numbering is according to SEQ ID NO: 13,-   G182*+D183*+N195F+A428T,-   G182*+D183*+N195F,-   H1*+G182*+D183*+N195F,-   N54S+G182*+D183*+N195F,-   V56T+G182*+D183*+N195F,-   G182*+D183*+N195F+I405L,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T+D476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476G,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477S;-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K,-   H1*+N54S+V56T+K72R+G109A+\Ail    67F+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L'S280Q+H321Y+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S304N+I405L+A421H+A422P+A428T+D476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476G+G477T,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422-   P+A428T+G477A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476N,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476Y,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206I+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+A204G+V206L+405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+A204G+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+G196R+V206L+G255A+I405L+A421H+A422P+A428T+N475S,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+T40D+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+N125D+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116Q+G133Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T+G448D,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+I405L    A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*D183*+N195F+V206L+S+A421H+A422P+A428T,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+M105F+G182*+D183*+N195F+V206L+L228I+R320A+S323N+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+V120L+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+O172N+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,    wherein numbering is according to SEQ ID NO: 14.

In one embodiment, the IF is determined by use of Model J detergent at atemperature of 15° C. In a particular embodiment, the variants have anIF of >1 as compared to the parent polypeptide, wherein the IF isdetermined by use of Model J detergent at a temperature of 15° C. and aconcentration of 0.05 mg/L. It can be seen from the Tables in theExamples herein disclosed which such variants may be.

In another embodiment, the variant has an IF of at least >1.5 whencompared to said parent polypeptide, and wherein said variant isselected from

-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T40G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37M+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37R+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+G142T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125P+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246T+K391A+G476K,-   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H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381A+K391A+G476K,-   H1*+N54S+V56T+G109A+W167I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420S+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420K+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420L+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473T+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444S+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444D+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280W+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255N+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q449T+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473K+G476K,-   H1*+N54S+V56T+K72S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T40K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A++Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484G,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484P,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484E,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484S,-   H1*K+G50A+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+Q98S+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+H324L+K391A+G476K,-   H1*+N54S+V56T+G109A+G149Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,-   H1*+N54S+V56T+G109AG255A++A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+F113L+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+G477Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q345D+K391A+G476K+G477Q,-   H1*+G50A+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264I+K391A+G423H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320V+K391A+G476Y,-   H1*+T5K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P211D+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444R+G476K,-   H1*+G50A+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204V+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+F113L+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K-   H1*+N54S+V56T+G109A+Q118G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280K+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,-   H1*+N54S+V56T+G109A+Q118S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+I134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G337H+Q385L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382M+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+M105F+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+Q118F+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+D377H+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q299V+K391A+G476K,-   H1*+N54S+V56T+G109A+L173G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I355L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+A174E+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+V56T+M105I+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246L+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+A174P+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72A+G109A+W167S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+Q11H+N54S+V56T+G109A+Q118R+T134E+A174S+G184I+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174Q+G182*+D183*+N195F+V206L+K391A+G476K+G477A,-   H1*+N54S+V56T+K72R+G109A+W167L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+F328L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+D377H+K391A+G476K;-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328V+D377H+K391A+G476K;-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291T+D377H+K391A+G476K;-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K;-   H1*+N54S+V56T+G109A+L173H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N16S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72N+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72N+G109A+W167L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72A+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182A+D183*+N195F+G184T+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,-   H1*+N54S+V56T+G109A+R116E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217    Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,-   H1*+N54S+V56T+G109A+R116S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377Q+K391A+G476K,-   H1*+N54S+V56T+G109A+R116I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174F+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+Q172M+A174S+G182*+D183*+N195F+V206L    K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+I51A+N54S+V56T+G109A+Q172A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172R+A174S+G182*4D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51D+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172R+A174S+K179E+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72M+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391S+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K391A+T444A+G476K,-   H1*+N54S+V56T+G109A+F113L+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+A174E+G182*+D183*+N195F+A204T+V206L+S323N+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183A+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A225F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382I+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214E+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+I214W+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204T+V206L+D377H+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204S+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T16 S A174S+G182A+D195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T334S+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A263G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N5F+V206L+M286F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182A+D183A+N195F+V206L+L235V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235A+D377H+K391A+G476K,-   H1*+N54S+V56T+M105L+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+M105I+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K    A+G476K,-   H1*+N54S+V56T+M105V+G109A+A174S+G182*4D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391M+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391E+G476K,-   H1*+N54S+V56T+G109A+T165G+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54L+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174V+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246S+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174L+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391D+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391W+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391I+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391Q+G476K,-   H1*+N54S+V56T+G109A+Q172H+L173A+A174P+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+W167R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F    V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376I+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173I+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+L173A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267H+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238G+K391A+G476K,-   H1*+N54S+V56T+M105V+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264I+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+K391A+G476K,-   H1*+N54S+V56T+G109A+W167H+Q172N+L173A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172E+L173P+A174K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+L173T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+L173V+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173F+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173T+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+L173V+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173M+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173F+A174P+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+Q172E+L173V+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250M+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204S+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T334S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A263G+M286L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391L+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*4D183*+N195F+i-\204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+A204G+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A265G+K391A+T444Q+G476K+G477A,-   H1*+A37V+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G346T+G477A+G476K,-   H1*+N54S+V56T+G109A+R116Q+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G346T+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109S+W167F+Q172R+A174S+G182*+D*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+V264I+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280Q+H321Y+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+F113Q+R6H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+R116H+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+F289I+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R6H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D*+N195F+V206L+A265G+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+T165G+A174S+G182*+D183+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51V+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280Q+H321Y+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+G133Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+Q395P+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+\N167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G173V+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172G+A174S+G182*+D1*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109S+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109S+F113Q+W167F+Q172R+A174S+G182    D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+A445Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+G133Q+W167F+Q172N+A74S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+A37H+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N5F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+67F+Q172N+A174S+G182    D183*+N195F+V206L+K391A+T459N+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F    V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116H+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+I173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116A+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L,-   N54S+V56T+G109A+G182*+D183*+N195F,-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*4N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+G476K,-   H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+G273R+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L,-   H1*+W48G+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F    V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+R116Q+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+V56A+G109A+A174S+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+G476K,-   G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   N54S+V56I+G109A+G182*+D183*+N195F+V206L+K391T+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109S+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G173V+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116H+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+K391A+G476K,-   H1*+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   G109A+G182*+D183*+N195F+V206L+G476K.-   H1*+G109A+G182K+D183*+N195F+K391A,-   H1*+N54S+V56T+G109A+G133S+A174S+G182*+D183*+N195F+K391A+G476H,-   H1A+N54S+V56T+G109A+R116A+Q172N+L173V+A174S+G182A+D18S+N195F+V206L+K391A+G476K.-   H1*+A37V+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+P45A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+P124A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+P364A+K391A+C474V+G476K.-   H1A+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+G184T+N195F+V206L+K391A+G476K,-   H1*+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+Y382L+K391A+G476K,-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+Q256A+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T165V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174N+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382F+K391A+G476K,-   H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q385L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+R171H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   G109A+G182*+D183*+N195F,-   G182*+D183*+N195F+K391A,-   H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R6Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172G+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184I+N195F+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116W+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+A186N+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A288V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270T+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A225V+K391A+G476K,-   H1*+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+Q169E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+W284H+K391A+G476K,-   H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+S304R+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G476K,-   F113Q+R116H+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A288L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   Q169E+Q172K+A174*+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   F113Q+R116Q+D183*+G182*+N195F,-   N54S+V56T+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   Q169E+Q172K+G182*+D183*+N195F,-   G182*+D183*+A186D,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,-   G182*+D183*+A186N,-   H1*+N54S+V56T+G109A+A174S+V206L+G182*+D183*+K391A+G476K,-   H1*+N54S+V56T+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F289L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   G182*+D183*+A186N+N195F,-   G182*+D183*+A186D+N195F,-   G182*+D183*+N195F+W284H,-   D183*+G182*+N195F+V326L,    wherein numbering is according to SEQ ID NO: 13, and-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476G+G477T,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476N,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476Y,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206I+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+T40D+N54S+V56T+G09A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+N125D+A174S+G195F+V296L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56I+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G173V+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+I4+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+F116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+V120L+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*    N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,    wherein numbering is according to SEQ ID NO: 14, and wherein the IF    is determined by use of Model A detergent.

In one embodiment, the IF is determined by use of Model A detergent at atemperature of 15° C. In a particular embodiment, the variants have anIF of >1.5 as compared to the parent polypeptide, wherein the IF isdetermined by use of Model A detergent at a temperature of 15° C. and aconcentration of 0.05 mg/L. It can be seen from the Tables in theExamples herein disclosed which such variants may be.

In another embodiment, the variant has an IF of at least 1.5 whencompared to the parent polypeptide and when determined by use of Model Jdetergent, wherein the variant is selected from the group consisting of:

-   G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T40 G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37M+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37Y+N54S+V56I+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37R+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+G142T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125P+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V213T+K391A+G476K,-   H1*+A37L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118K+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377R+K391A+G476K,-   H1+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381A+K391A+G476K,-   H1*+N54S+V56T+G109A+W167I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214T+K391A+G476K,-   H1+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420S+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420K+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420L+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473T+G476K,-   H1+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444S+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444D+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444    Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280W+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280L+K391A+G476K,-   H1+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255N+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q449T+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473K+G476K,-   H1*+N54S+V56T+K72S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T40K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A++Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484G,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484P,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484E,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484S,-   H1*K+G50A+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+Q98S+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+H324L+K391A+G476K,-   H1*+N54S+V56T+G109A+G149Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,-   H1*+N54S+V56T+G109AG255A++A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+F113L+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+G477Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q345D+K391A+G476K+G477Q,-   H1*+G50A+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264I+K391A+G423H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320V+K391A+G476Y,-   H1*+T5K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P211D+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444R+G476K,-   H1*+G50A+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204V+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+F113L+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280K+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,-   H1*+N54S+V56T+G109A+Q118S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G337H+Q385L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382M+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G    A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+M105F+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+Q118F+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+D377H+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q299V+K391A+G476K,-   H1*+N54S+V56T+G109A+L173G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T355L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T355F+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+A174E+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+V56T+M105k-G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246L+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+A174M+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+Q11H+N54S+V56T+G109A+Q118R+T134E+A174S+G184T+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*4N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174Q+G182*+D183*+N195F+V206L+K391A+G476K+G477A,-   H1*+N54S+V56T    K72A+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167S+G182*+D183*+N195F+A174S+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T    K72R+G109A+\A/167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291    G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+F328L+D377H+K391A+G476K,-   H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G47-   6K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328H-D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291    T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+L173H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N16S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72N+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72N+G109A+W167L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72A+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+G184T+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377R+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,-   H1*+N54S+V56T+G109A+R116E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346D+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,-   H1*+N54S+V56T+G109A+I134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,-   H1*+N54S+V56T+G109A+R116S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377Q+K391A+G476K,-   H1*+N54S+V56T+G109A+R116I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174F+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51D+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72M+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174Q+G182*4D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391S+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444A+G476K,-   H1*+N54S+V56T+G109A+F113L+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+A174E+G182*+D183*+N195F+A204T+V206L+S323N+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A225F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382I+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214E+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214W+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204T+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204S+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T165S+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T334S+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A263G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M286F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N5F+V206L+L235A+D377H+K391A+G476K,-   H1*+N54S+V56T+M105L+G109A+A174S+G182    D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+M105I+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+M105V+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+M246I+D377H+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K391V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391M+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391E+G476K,-   H1*+N54S+V56T+G109A+T165G+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K.-   H1*+N54S+V56T+G109S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174V+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246S+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174L+G182*+D183*+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391D+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391W+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391I+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L    L250M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391Q+G476K,-   H1*+N54S+V56T+G109A+Q172H+L173A+A174P+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173A+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A-1-W167R-1-A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184I+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T    K72R+G109A+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173I+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+L173A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267H+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238G+K391A+G476K,-   H1*+N54S+V56T+M105V+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264I+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+K391A+G476K,-   H1*+N54S+V56T+G109A+W167H+Q172N+L173A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172E+L173P+A174K+G182*+D*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+L173T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+L173V+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173F+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173    T+A174R+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+Q172N+L173V+A174R+G182*+D183*+N195F    V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174R+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+Q172E+L173M+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173F+A174P+G182*+D1*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+Q172E+L173V+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+L250F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250M+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+A204S+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I334S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A263G+M286L+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+Y267I+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+K391L+G476K-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1A+N54S+V56T+K72R+G109A+T134E+A174S+G182A+D183*+N195F+A204G+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K.-   H1A+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+C474V+G476K,-   H1A+N54S+V56T+G109A+I134E+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+D377H+K391A+C474V+G476K-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A265G+K391A+T444Q+G476K+G477A,-   H1*+A37V+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G346T+G477A+G476K.-   H1*+N54S+V56T+G109A+R116Q+Q172D+A174S+G182K+D183*+N195F+V206L+G346T+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+A174S+G182*+D183A+N195F+V206L+G346T+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109S+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+V264I+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F    V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280Q+H321    Y+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+R116H+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+F289I+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1+N54S+V56T+G109A+F113Q+R    H+T165G+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+A265G+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+T165G+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51V+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280Q+H321Y+K391A+G476K,-   H1+N54S+V56T+G109A+F113Q+R    H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+G133Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+Q395P+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172N+L173V+A174S+G182*+D183N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109S+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109S+F113Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+A445Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+i-\265G+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+G133Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+A37H+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+T459N+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116H+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56I+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+67F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*4D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116A+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L,-   N54S+V56T+G109A+G182*+D183*+N195F,-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+G476K,-   H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+G273R+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L,-   H1*+W48G+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A,-   H1*+N54S+V56T+G109A+F113Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+R116Q+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+V56A+G109A+A174S+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+G476K,-   G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391T+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109S+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116H+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+I165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1A+A37H+N54S+V56T+G109A+R116H+T165 G+A174    S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,-   H1*+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   G109A+G182*+D183*+N195F+V206L+G476K.-   H1*+G109A+G182*+D183A+N195F+K391A,-   H1*+N54S+V56T+G109A+G133S+A174S+G182*+D183*+N195F+K391A+G476H,-   H1*+N54S+V56T+G109A+R116A+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+P45A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K.-   H1*+N54S+V56T+G109A+P124A+A174S+G182*+D183K+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+P364A+K391A+C474V+G476K.-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1A+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+Y382L+K391A+G476K,-   H1*+G7K+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+Q256A+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+A174S+G182*+D183*+N195F+V206L K391A+G476K.-   H1A+N54S+V56T+G109A+W167H+A174S+G182A+D183A+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T165V+A174S+G182K+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174N+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382F+K391A+G476K,-   H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q385L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+R171H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   N54S+G182*+D183*+N195F,-   G109A+G182*+D183*+N195F,-   G182*+D183*+N195F+G476K,-   H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172G+A174*+G182*+D183*+N195F+V206L+K    A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116W+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+A186N+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A288V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270T+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G478K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A225V+K391A+G476K,-   H1*+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+Q169E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+W284H+K391A+G476K,-   H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+S304R+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G476K,-   F113Q+R116H+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A288L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   Q169E+Q172K+A174*+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   F113Q+R116Q+D183*+G182*+N195F,-   N54S+V56T+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*4N195F+V206L+K391A+G476K,-   Q169E+Q172K+G182*+D183*+N195F,-   G182*+D183*+A186D,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,-   G182*+D183*+A186N,-   H1*+N54S+V56T+G109A+A174S+V206L+G182*+D183*+K391A+G476K,-   H1*+N54S+V56T+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F289L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S244Q+K391A+G476K,-   G182*+D183*+F328L,-   G182*+D183*+N195F+A288V,-   G182*+D183*+A186N+N195F,-   G182*+D183*+E190P+N195F,-   W140Y+G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A225V+K391A+G476K,-   G182*+D183*+A186D+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+W48Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F+V238A,-   G182*+D183*+Y295N,-   Q172G+G182*+D183*,-   F113Q+G182*+D183*+N195F,-   H1*+N54S+V56T+Q98A+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F+Y295F,-   G182*+D183*+A186E,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206Y+K391A+G476K,-   G182*+D183*+N195F+W284H,-   G182*+D183*+A186Q+N195F,-   K72R+G182*+D183*,-   D183*+G182*+N195F+V326L,-   D183*+G182*+A186E+N195F,-   Q169E+G182*+D183*+N195F,-   D183*+G182*+N195F+K242Q,-   G7A+G182*+D183*+N195F,-   D183*+G182*+N195F+N260G,-   D183*+G182*+R321A+S323N,-   D183*+G82*+W284H,-   D183*+G182*+A186H+N195F,-   D183*+G182*+K391A.-   wherein numbering is according to SEQ ID NO: 13,-   V56T+G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G INA-FRI    74S+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+G182*+D163*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477S,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476G+G477T,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476N,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476Y,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206I+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+A204G+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*4N195F+G196R+V206L+G255A+405L+A421H+A422P+A428T+N475S,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+T40D+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+N125D+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T.-   H1*+N54S+V56T+G109A+R116Q+G133Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T+G448D,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+i-\265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+L173V+A74S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172G+A174S+G    D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+A174S+M105F+G182*+D183*+N195F+V206L+L228I+R320A+S323N+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+V120L+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1+A37H+N54S+V56T+A60V+G109A+R116Q+\N167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,    wherein numbering is according to SEQ ID NO: 14.

In one embodiment, the IF is determined by use of Model J detergent at atemperature of 15° C. In a particular embodiment, the variants have anIF of >1.5 as compared to the parent polypeptide, wherein the IF isdetermined by use of Model J detergent at a temperature of 15° C. and aconcentration of 0.05 mg/L. It can be seen from the Tables in theExamples herein disclosed which such variants may be.

Some variants according to the invention have an even further improvedwash performance indicated by an IF of at least 2.0 when compared the aparent polypeptide having an amino acid sequence set forth in SEQ ID NO:15, and wherein the IF is determined by use of Model A detergent at atemperature of 15° C.

Thus, in one embodiment, the variant has an IF of at least >2.0 whencompared to said parent polypeptide, and wherein said variant isselected from

-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T40G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1+A37H+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37M+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37R+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1+N54S+V56T+G109A+F113S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125P+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246T+K391A+G476K,-   H1*+A37L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172R+A174S+G182*4D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420S+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420K+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420L+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444D+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280W+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T40K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A++C)    172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484S,-   H1*K+G50A+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,-   H1*+N54S+V56T+G109AG255A++A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+G50A+N54S+V56T+G109A+F113L+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320V+K391A+G476Y,-   H1*+N54S+V56T+G109A+R116M+A174S+G182K+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+I214L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+P211D+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Q+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444R+G476K,-   H1*+G50A+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204V+V206L+K391A+G476K.-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+R320A+K391A+G476K-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,-   H1*+N54S+V56T+G109A+Q118S+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+Y382M+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K.-   H1*+N54S+V56T+K72R+M105F+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1A+N54S+V56T+M105F+G109A+I134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+D377H+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+L173A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q299V+K391A+G476K-   H1*+N54S+V56T+G109A+L173G+A174S+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T355L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1A+N54S+V56T+K72R+G109A+A174S+G182A+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T    K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183A+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174Q+G182*+D183*+N195F+V206L+K391A+G476K+G477A,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A74S+G182*+D183A+G184T+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+L173H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72N+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72N+G109A+W167L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+G184T+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,    H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,-   H1*+N54S+V56T+G109A+R116E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+R116S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172L+A174S+G2*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K721V1+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1A+G50A+N54S+V56T+G109A+A174E+G182*+D183*+N195F+A204T+V206L+S323N+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382I+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214W+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+A204S+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T334S+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A263G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M286F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+D377H+K391A+G476K,-   H1*+N54S+V56T+M105L+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1A+N54S+V56T+M105I+G109A+A174S+G182*+D183*+N195F    V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+M105V+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391Y+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+K391M+G476K,-   H1*+N54S+V56T+G109A+T165G+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174V+G182*+D183A+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+M246V+D377H+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246S+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391W+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183+N195F+V206L+K391I+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+L250A+D377H+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183+N195F+V206L+L250M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172H+L173A+A174P+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+S376T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173I+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+L173A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238G+K391A+G476K,-   H1*+N54S+V56T+M105V+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264I+K391A+G476K,-   H1*+N54S+V56T+G109A+W167H+Q172N+L173A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+L173T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173M+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+Q172E+L173V+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250M+K391A+G476K,-   H1*+N54S+V56T+G109A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391L+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+04G+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183A+N195F+V206L+R320A+S323N+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182+D183*4N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+A265G+K391A+T444Q+G476K+G477A,-   H1*+A37V+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G346T+G477A+G476K,-   H1*+N54S+V56T+G109A+R116Q+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G346T+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+W167F+Q172G+A174S+G182*+D183A+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+G109A+F113Q+Q172G+A174S+G182*+D183*+N195F    V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*4N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+V264I+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280Q+H321Y+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+R116H+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+F289I+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R6H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+A265G+K    A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N19F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+T165G+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51V+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280Q+H321Y+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+G133Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+Q395P+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182    D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172G+A174S+G182*+D1*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109S+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109S+F113Q+W167F+Q172R+A174S+G182    D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+73V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+I444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+G133Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+A37H+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183A+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183+N195F+V206L+K391A+T459N+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116H+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183A+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F    V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+k    167F+Q172R+A174S+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116A+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+T165    G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L,-   N54S+V56T+G109A+G182*+D183*+N195F,-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+G476K,-   H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+G273R+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L,-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+R116Q+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116C)+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+V56A+G109A+A174S+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109S+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+\N167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116H+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+G133S+A174S+G182*+D183*+N195F+K391A+G476H,-   H1*+N54S+V56T+G109A+R116A+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+P45A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P364A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382L+K391A+G476K,-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+Q256A+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T165V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382F+K391A+G476K,-   H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q385L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+R171H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172G+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116W+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+A186N+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A288V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270T+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A225V+K391A+G476K,-   H1*+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G2    S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,    wherein numbering is according to SEQ ID NO: 13, and-   H1*+T40D+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T-   H1*+N54S+V56T+G109A+F113Q+N125D+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+I405L+A421H+A422P+A428T-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T-   H1*+N54S+V56T+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+V120L+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183F+V206L+A265G+I405L+A421H+A422P+A428T-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,    wherein numbering is according to SEQ ID NO: 14, and wherein the IF    is determined by use of Model A detergent.

In one embodiment, the variant has an IF of at least 2.0 when comparedto the parent polypeptide, wherein the IF is determined by use of ModelA detergent at a temperature of 15° C. and a concentration of 0.05 mgenzyme/L.

In one embodiment, the variant has an IF of at least 2.0 when comparedto the parent polypeptide and when determined by use of Model Jdetergent, and wherein the variant is selected from the group consistingof:

-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T40G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37M+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37R+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125P+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V213T+K391A+G476K,-   H1*+A37L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377R+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214G+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381A+K391A+G476K,-   H1*+N54S+V56T+G109A+W167I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420S+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420K+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420L+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473T+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444S+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444D+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K391A+T444Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280W+K391A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+S280T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255N+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285L+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+T285Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473K+G476K,-   H1*+N54S+V56T+K72S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+T40K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K.-   H1A+G50A+N54S+V56T+G109A++Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484G-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484P.-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K391A+G476K+K484E,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484Q-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484S.-   H1*K+G50A+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1A+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+Q98S+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+H324L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,-   H1*+N54S+V56T+G109AG255A++A174S+G182K+D183*+N195F+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+F113L+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+G477Q,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q345D+K391A+G476K+G477Q,-   H1*+G50A+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264I+K391A+G423H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320V+K391A+G476Y,-   H1*+N54S+V56T+G109A+R116M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P211D+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Q+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444V+G476K,-   H1*+G50A+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204V+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+F113L+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382M+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*4N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+M105F+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+D377H+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173A+A174S+G182*4D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+Q299V+K391A+G476K,-   H1*+N54S+V56T+G109A+L173G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I355L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+A174S+G182*+D183K+N195F+A204T+V206L+K391A+G476K.-   H1*+G50A+N54S+V56T+G109A+A174E+G182*+D183*+N195F+A204T+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+T51G+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1A+Q11H+N54S+V56T+G109A+Q1R    T134E+A174S+G184T+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183.*+G184T+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1A+N54S+V56T+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A74S+G182*+D183A+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174Q+G182*+D183*+N195F+V206L+K391A+G476K+G477A,-   H1*+N54S+V56T+K72R+G109A+W167L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183+N195F+V206L+G255A+D377H+K391A+G476K-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+F328L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L    V238G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F328I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D1*+G184T+N195F    V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+L173H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N16S+N54S+V56T+G109A+A174S+G182*+D183*4N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72N+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+G184T+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+A174S+G182*+D183*+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,-   H1*+N54S+V56T+G109A+R116E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,-   H1*+N54S+V56T+G109A+R116S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377Q+K391A+G476K,-   H1*+N54S+V56T+G109A+R116I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51S+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51A+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51E+N54S+V56T+G109A+Q172L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72H+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72M+G109A+Q172S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72Q+G109A+A174G+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72S+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444A+G476K,-   H1*+N54S+V56T+G109A+F113L+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214E+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214W+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+A204T+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+A204S+V206L+D377H+K391A+G476K.-   H1A+N54S+V56T+G109A+I165S+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T334S+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A263G+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M286F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+D377H+K391A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235A+D377H+K391A+G476K,-   H1*+N54S+V56T+M105L+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+M105I+G109A+A174S+G182*+D183.*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+M105V+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246I+D377H+K391A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250I+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183+N195F+V206L    L250V+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391Y+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183+N195F+V206L+K391V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391M+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391E+G476K,-   H1*+N54S+V56T+G109A+T165G+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174V+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182A+D183+N195F+V206L+M246F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174L+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+K391D+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391R+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391H+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+K391W+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391I+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250T+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+L250A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250F+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172H+L173A+A74P+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183+G184T+N195F+V206L+G255A+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S376T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+S376V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173I+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+L173A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267M+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183+N195F+V206L+Y267H+D377H+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+V238G+K391A+G476K,-   H1*+N54S+V56T+M105V+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264T+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264I+K391A+G476K.-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+L235V+K391A+G476K,-   H1*+N54S+V56T+G109A+W167H+Q172N+L173A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172E+L173P+A174K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+L173T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173F+A174R+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109A+Q172E+L173T+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+L173V+A174R+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173M+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172E+L173F+A174P+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+Q172E+L173V+A174H+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+L173A+A174T+G182K+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+L250V+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250F+K391A+G476K.-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250M+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T334S+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A263G+M286L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267H+K391A+G476K,-   H1A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y267L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182K+D183*+N195F+V206L+K391L+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*4N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+A204G+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+G184T+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,-   H1*+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182*+D183K+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183A+N195F+V206L+R320A+S323N+K391A+C474V+G476K.-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*4N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183A+N195F+V206L+A265G+K391A+T444Q+G476K+G477A.-   H1A+A37V+N54S+V56T+G109A+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G346T+G477A+G476K,-   H1*+N54S+V56T+G109A+R116Q+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G346I+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109S+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+V264I+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280Q+H321Y+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R6Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+R116H+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D1*+N195F+V206L+F289I+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+A265G+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+T165G+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+V2-   06L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+T51V+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280Q+H321Y+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R6H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+G133Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+Q395P+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109S+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109S+F113Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+A445Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+G133Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+A37H+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+\Ail    67F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+T459N+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172R+L173V+A74S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116H+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G478K,-   H1*+A37V+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116A+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+G182*+D N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L,-   N54S+V56T+G109A+G182*+D183*+N195F,-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+G476K,-   H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+G273R+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L,-   H1*+W48G+G109A+G182*+D183*+N195F+V206L+K391A+G476K,-   N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A,-   H1*+N54S+V56T+G109A+F113Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+R116Q+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D1+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+V56A+G109A+A174S+G182*+D183*4N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109S+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+67F+Q172R+A174S+G182*+D1*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+R116H+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,-   G109A+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+G133S+A174S+G182*+D183*+N195F+K391A+G476H,-   H1*+N54S+V56T+G109A+R116A+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+P45A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+P124A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P364A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382L+K391A+G476K,-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+Q256A+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T165V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382F+K391A+G476K,-   H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q385L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+R171H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172G+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116W+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*4N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q72K+A174*+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+A186N+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A288V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270T+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+A186D+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A225V+K391A+G476K,-   H1*+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255S+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   G182*+D183*+N195F,-   H1*+N54S+V56T+G109A+Q169E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+W284H+K391A+G476K,-   H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+S304R+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+W140Y+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+F328L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G476K,-   F113Q+R116H+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A288L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K,-   Q169E+Q172K+A174*+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   F113Q+R116Q+D183*+G182*+N195F,-   N54S+V56T+D183*+G182*+N195F,-   H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   Q169E+Q172K+G182*+D183*+N195F,-   G182*+D183*+A186D,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,-   G182*+D183*+A186N,    wherein numbering is according to SEQ ED NO: 13,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206I+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+A204G+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+G196R+V206L+G255A+I405L+A421H+A422P+A428T+N475S,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+N125D+A174S+G182+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+R116Q+G133Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T+G448D;-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182    D183*+N195F+V206L+G255A+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+K72R+G109A+R116Q+V120L+A174S+G182*+D1    G184T+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A26-   5G+I405L+A421H+A422P+A428T,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,    wherein numbering is according to SEQ ID NO: 14.

In one embodiment, the variant has an IF of at least 2.0 when comparedto the parent polypeptide, wherein the IF is determined by use of ModelJ detergent at a temperature of 15° C. and an enzymes concentration of0.05 mg/L.

Other variants according to the invention have an IF of at least 3.0,indicating that at least these variants have a significantly improvedwash performance when compared the a parent polypeptide having an aminoacid sequence set forth in SEQ ID NO: 15.

In a particular embodiment, the variant is selected from a groupconsisting of:

-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+G133Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,    and-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+T444Q+P473R+G476K,    wherein numbering is according to SEQ ID NO: 13.

In another embodiment, the variant has an IF of at least 3.0 whencompared to the parent polypeptide and determined by use of Model Jdetergent, and wherein the variant is selected from the group consistingof:

-   H1*+T51K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q125A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444D+G476K,-   H1*+N54S+V56T+K72S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+G50A+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204V+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+G184T+N195F    V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+D377H+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174Q+G182*+D183*+N195F+V206L+K391A+G476K+G477A,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*4N195F+G184T+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238G+K391A+G476K,-   H1A+N54S+V56T+G109A+W167F+Q172E+L173P+A174K+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L250M+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K.-   H1*+N54S+V56T+G109S+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+A204G+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+R116Q+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+T444Q+G477A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172N+A174S+G182*+D183A+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+G109S+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172G+A174S+G182*4D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q172N+A174S+G182*+D183*+N195F+V206L+V264I+K391A+C474V+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+Q172N+A174S+G182*+D183*+N195F+V206L    K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+T165G+A174S+G182*+D1+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R6H+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+G133Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+Q395P+K391A+G476K,-   H1*+A37V+N54S+V56T+K72R+G109A+R116H+W167F+Q172R+A174S+G182    D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109S+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109S+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109S+F113Q+W167F+Q172R+A174S+G182*+D183*N195F+V206L+K391A+G476K-   H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+T134E+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+G255A+K391A+T444Q+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182K+D183*+N195F+V206L+G255A+A265G+K391A+T444Q+P473R+G476K,-   H1+N54S+V56T+K72R+G109A+G133Q+W167F+Q172R    A74S+G182*+D183A+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L    K391A+P473R+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116H+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,-   H1+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+L173V    A74S+G182A+D183*+N195F+V206L+K391A+G476K,-   H1A+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K-   H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+R116Q+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*4N195F+V206L+K391A+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109S+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,-   H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+A37H+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,-   H1*+N54S+V56T+G109A+R116A+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+P45A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,-   H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264F+K391A+G476K,-   H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+Q256A+K391A+G476K,-   H1*+N54S+V56T+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182A+D183*+N195F+V206L+Y382F+K391A+G476K,-   H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q385L+K391A+G476K,-   H1*+N54S+V56T+R87S+G109A+R171H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R6Q167F+Q172G    A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172G+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+R116W+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206F+K391A+G476K,-   H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+G184T+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,-   H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+A186N+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A288V+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255A+K391A+G476K,-   H1*+N54S+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+W48F+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q72K+A174*+G182*+D183*+N195F+V206L+V291A+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,-   H1*+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F    V206L+K391A+G476K,-   H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,-   H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270T+K391A+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G476K,-   H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N260G+K391A+G476K,-   H1*+N54S+V56T+G109A+F113Q+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,    wherein numbering is according to SEQ ID NO: 13,-   H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,-   H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,    wherein numbering is according to SEQ ID NO: 14.

The variants according to the present invention may further comprise oneor more additional alterations than those described above at one or more(e.g., several) other positions.

The amino acid changes may be of a minor nature, that is conservativeamino acid substitutions or insertions that do not significantly affectthe folding and/or activity of the protein: small deletions, typicallyof 1-30 amino acids; small amino- or carboxyl-terminal extensions, suchas an amino-terminal methionine residue; a small linker peptide of up to20-25 residues; or a small extension that facilitates purification bychanging net charge or another function, such as a poly-histidine tract,an antigenic epitope or a binding domain.

Examples of conservative substitutions are within the groups of basicamino acids (arginine, lysine and histidine), acidic amino acids(glutamic acid and aspartic acid), polar amino acids (glutamine andasparagine), hydrophobic amino acids (leucine, isoleucine and valine),aromatic amino acids (phenylalanine, tryptophan and tyrosine), and smallamino acids (glycine, alanine, serine, threonine and methionine). Aminoacid substitutions that do not generally alter specific activity areknown in the art and are described, for example, by H. Neurath and R. L.Hill, 1979, in, The Proteins, Academic Press, New York. Commonsubstitutions are Ala/Ser, Val/Ile, Asp/Glu, Thr/Ser, Ala/Gly, Ala/Thr,Ser/Asn, Ala/Val, Ser/Gly, Tyr/Phe, Ala/Pro, Lys/Arg, Asp/Asn, Leu/Ile,Leu/Val, Ala/Glu, and Asp/Gly.

Alternatively, the amino acid changes are of such a nature that thephysico-chemical properties of the polypeptides are altered. Forexample, amino acid changes may improve the thermal stability of thepolypeptide, alter the substrate specificity, change the pH optimum, andthe like.

Essential amino acids in a polypeptide may be identified according toprocedures known in the art, such as site-directed mutagenesis oralanine-scanning mutagenesis (Cunningham and Wells, 1989, Science 244:1081-1085). In the latter technique, single alanine mutations areintroduced at every residue in the molecule, and the resultant mutantmolecules are tested for alpha-amylase activity to identify amino acidresidues that are critical to the activity of the molecule. See also,Hilton et al., 1996, J. Biol. Chem. 271: 4699-4708. The active site ofthe enzyme or other biological interaction can also be determined byphysical analysis of structure, as determined by such techniques asnuclear magnetic resonance, crystallography, electron diffraction, orphotoaffinity labeling, in conjunction with mutation of putative contactsite amino acids. See, for example, de Vos et al., 1992, Science 255:306-312; Smith et al., 1992, J. Mol. Biol. 224: 899-904; Wlodaver etal., 1992, FEBS Lett. 309: 59-64. The identity of essential amino acidscan also be inferred from an alignment with a related polypeptide.

The variants according to the present invention may consist of 400 to485 amino acids, e.g., 410 to 485, 425 to 485, and 440 to 485 aminoacids.

Polynucleotides

The present invention also relates to polynucleotides encoding a variantof the present invention. Thus, in particular, the present inventionrelates to a polynucleotide endocing a variant comprising an alterationin one or more positions corresponding to the H1, T5, G7, Q11, N16, V17,Q32, A37, T40, P45, W48, G50, T51, N54, V56, K72, R87, Q98, M105, G109,F113, R116, Q118, Q125, G133, T134, W140, G142, G149, T165, W167, Q169,R171, Q172, L173, A174, G184, A186, E190, T193, N195, A204, V206, P211,I214, V215, L217, L219, A225, L235, V238, K242, S244, M246, M248, L250,G255, Q256, N260, A263, V264, Y267, K269, N270, G273, S280, W284, T285,M286, F289, V291, Y295, Q299, R320, H321, S323, H324, V326, F328, T334,D337, Q345, G346, G348, T355, S376, D377, D379, Y382, S383, Q385, K391,K393, Q395, A420, G423, T444, A445, Q449, T459, P473, C474, G476, G477,and K484 of SEQ ID NO: 13; or H1, A37, T40. N54, V56, A60, K72, G109,F113, R116, N125, F133, T134, T165, Q169, Q172, L173, A174, G184, A186,E190, N195, G196, A204, V206, A225, L228, K242, S244, G255, N260, A265,K269, S280. W284, S304, R320, H321, S323, V326, K391, I405, A421, A422,A428, G448, D476, and G477 of SEQ ID NO: 14.

The term “polynucleotides encoding” as used herein, refers to apolynucleotide that encodes a mature polypeptide having alpha-amylasehaving alpha-amylase activity. In one aspect, the polypeptide codingsequence is the nucleotide sequence set forth in SEQ ID NO: 1, 2, or 3.

In one embodiment, the polynucleotide encoding a variant according tothe present invention as at least 60%, such as at least 65%, such as atleast 70%, such as at least 75%, such as at least 80%, such as at least85%, such as at least 90%, such as at least 95%, such as at least 96%,such as at least 97%, such as at least 98%, such as at least 99% butless than 100% sequence identity to the polynucleotide of SEQ ID NOs: 1,2 and 3.

Nucleic Acid Constructs

The present invention also relates to nucleic acid constructs comprisinga polynucleotide encoding a variant of the present invention operablylinked to one or more control sequences that direct the expression ofthe coding sequence in a suitable host cell under conditions compatiblewith the control sequences. Thus, in particular, the present inventionrelates to a nucleic acid construct comprising a polynucleotide encodinga variant comprising an alteration in one or more positionscorresponding to the positions H1 T5, G7, Q11, N16, V17, Q32, A37, T40,P45, W48, G50, T51, N54, V56, K72, R87, Q98, M105, G109, F113, R116,Q118, Q125, G133, T134, W140, G142, G149, T165, W167, Q169, R171, Q172,L173, A174, G184, A186, E190, T193, N195, A204, V206, P211, I214, V215,L217, L219, A225, L235, V238, K242, S244, M246, M248, L250, G255, Q256,N260, A263, V264, Y267, K269, N270, G273, S280, W284, T285, M286, F289,V291, Y295, Q299, R320, H321, S323, H324, V326, F328, T334, D337, Q345,G346, G348, T355, S376, D377, D379, Y382, S383, Q385, K391, K393, Q395,A420, G423, T444, A445, Q449, T459, P473, C474, G476, G477, and K484 ofSEQ ID NO: 13; or H1, A37, T40, N54, V56, A60, K72, G109, F113, R116,N125, F133, T134, T165, Q169, Q172, L173, A174, G184, A186, N195, G196,A204, V206, A225, L228, K242, S244, G255, N260, A265, K269, S280, W284,Y295, S304, R320, H321, S323, V326, K391, I405, A421, A422, A428, R439,G448, W467, D476, and G477 of SEQ ID NO: 14, wherein the polynucleotideis operately linked to one or more control sequences.

The term “nucleic acid construct” as used herein, refers to a nucleicacid molecule, either single- or double-stranded, which is isolated froma naturally occurring gene or is modified to contain segments of nucleicacids in a manner that would not otherwise exist in nature or which issynthetic, which comprises one or more control sequences.

The term “operably linked” as used herein, refers to a configuration inwhich a control sequence is placed at an appropriate position relativeto the coding sequence of a polynucleotide such that the controlsequence directs expression of the coding sequence.

The polynucleotide may be manipulated in a variety of ways to providefor expression of a variant. Manipulation of the polynucleotide prior toits insertion into a vector may be desirable or necessary depending onthe expression vector. The techniques for modifying polynucleotidesutilizing recombinant DNA methods are well known in the art.

The control sequence may be a promoter, a polynucleotide which isrecognized by a host cell for expression of the polynucleotide. Thepromoter comprises transcriptional control sequences that mediate theexpression of the variant. The promoter may be any polynucleotide thatshows transcriptional activity in the host cell including mutant,truncated, and hybrid promoters, and may be obtained from genes encodingextracellular or intracellular polypeptides either homologous orheterologous to the host cell.

Expression Vectors

The present invention also relates to recombinant expression vectorscomprising a polynucleotide encoding a variant of the present invention,a promoter, and transcriptional and translational stop signals. Thus,the present invention relates to an expression vector, optionallyrecombinant, comprising a polynucleotide encoding a variant comprisingan alteration in one or more positions corresponding to the positionsH1, T5, G7, Q11, N16, V17, Q32, A37, T40, P45, W48, G50, T51, N54, V56,K72, R87, Q98, M105, G109, F113, R116, Q118, Q125, G133, T134, W140,G142, G149, T165, W167, Q169, R171, Q172, L173, A174, G184, A186, E190,T193, N195, A204, V206, P211, I214, V215, L217, L219, A225, L235, V238,K242, S244, M246, M248, L250, G255, Q256, N260, A263, V264, Y267, K269,N270, G273, S280, W284, T285, M286, F289, V291, Y295, Q299, R320, H321,S323, H324, V326, F328, T334, D337, Q345, G346, G348, T355, S376, D377,D379, Y382, S383, Q385, K391, K393, Q395, A420, G423, T444, A445, Q449,T459, P473, C474, G476, G477, and K484 of SEQ ID NO: 13; or H1, A37,T40, N54, V56, A60, K72, G109, F113, R116, N125, F133, T134, T165, Q169,Q172, L173, A174, G184, A186, N195, G196, A204, V206, A225, L228, K242,S244, G255, N260, A265, K269, S280, W284, Y295, S304, R320, H321, S323,V326, K391, I405, A421, A422, A428, R439, G448, W467, D476, and G477 ofSEQ ID NO: 14, a promoter, and transcriptional and translational stopsignals.

The term “expression vector” as used herein, refers to a linear orcircular DNA molecule that comprises a polynucleotide encoding a variantand is operably linked to control sequences that provide for itsexpression.

The various nucleotide and control sequences may be joined together toproduce a recombinant expression vector that may include one or moreconvenient restriction sites to allow for insertion or substitution ofthe polynucleotide encoding the variant at such sites. Alternatively,the polynucleotide may be expressed by inserting the polynucleotide or anucleic acid construct comprising the polynucleotide into an appropriatevector for expression. In creating the expression vector, the codingsequence is located in the vector so that the coding sequence isoperably linked with the appropriate control sequences for expression.

The recombinant expression vector may be any vector (e.g., a plasmid orvirus) that can be conveniently subjected to recombinant DNA proceduresand can bring about expression of the polynucleotide. The choice of thevector will typically depend on the compatibility of the vector with thehost cell into which the vector is to be introduced. The vector may be alinear or closed circular plasmid.

The vector may be an autonomously replicating vector, i.e., a vectorthat exists as an extrachromosomal entity, the replication of which isindependent of chromosomal replication, e.g., a plasmid, anextrachromosomal element, a minichromosome, or an artificial chromosome.The vector may contain any means for assuring self-replication.Alternatively, the vector may be one that, when introduced into the hostcell, is integrated into the genome and replicated together with thechromosome(s) into which it has been integrated. Furthermore, a singlevector or plasmid or two or more vectors or plasmids that togethercontain the total DNA to be introduced into the genome of the host cell,or a transposon, may be used.

The vector preferably contains one or more selectable markers thatpermit easy selection of transformed, transfected, transduced, or thelike cells. A selectable marker is a gene the product of which providesfor biocide or viral resistance, resistance to heavy metals, prototrophyto auxotrophs, and the like.

The skilled person would know which expression vector is the mostsuitable for specific expression systems. Thus, the present invention isnot limited to any specific expression vector, but any expression vectorcomprising the polynucleotide encoding a variant according to theinvention is considered part of the present invention.

Host Cells

The present invention also relates to recombinant host cells, comprisinga polynucleotide encoding a variant of the present invention operablylinked to one or more control sequences that direct the production of avariant of the present invention. Thus, the present invention relates toa host cell, optionally a recombinant host cell, comprising apolynucleotide encoding a variant comprising an alteration in one ormore positions corresponding to the positions H1, T5, G7, Q11, N16, V17,Q32, A37, T40, P45, W48, G50, T51, N54, V56, K72, R87, Q98, M105, G109,F113, R116, Q118, Q125, G133, T134, W140, G142, G149, T165, W167, Q169,R171, Q172, L173, A174, G184, A186, E190, T193, N195, A204, V206, P211,I214, V215, L217, L219, A225, L235, V238, K242, S244, M246, M248, L250,G255, Q256, N260, A263, V264, Y267, K269, N270, G273, S280, W284, T285,M286, F289, V291, Y295, Q299, R320, H321, S323, H324, V326, F328, T334,D337, Q345, G346, G348, T355, S376, D377, D379, Y382, S383, Q385, K391,K393, Q395, A420, G423, T444, A445, Q449, T459, P473, C474, G476, G477,and K484 of SEQ ID NO: 13; or H1, A37, T40, N54, V56, A60, K72, G109,F113, R116, N125, F133, T134, T165, Q169, Q172, L173, A174, G184, A186,E190, N195, G196, A204, V206, A225, L228, K242, S244, G255, N260, A265,K269, S280, W284, Y295, S304, R320, H321, S323, V326, K391, I405, A421,A422, A428, R439, G448, W467, D476, and G477 of SEQ ID NO: 14, operablylinked to one or more control sequences that direct the production ofthe variant.

The term “host cell” as used herein, refers to any cell type that issusceptible to transformation, transfection, transduction, or the likewith a nucleic acid construct or expression vector comprising apolynucleotide of the present invention. The term “host cell”encompasses any progeny of a parent cell that is not identical to theparent cell due to mutations that occur during replication.

A construct or vector comprising a polynucleotide is introduced into ahost cell so that the construct or vector is maintained as a Chromosomalintegrant or as a self-replicating extra-chromosomal vector as describedearlier. The choice of a host cell will to a large extent depend uponthe gene encoding the variant and its source.

The host cell may be any cell useful in the recombinant production of avariant, e.g., a prokaryote or a eukaryote.

The prokaryotic host cell may be any Gram-positive or Gram-negativebacterium. Gram-positive bacteria include, but are not limited to,Bacillus, Clostridium, Enterococcus, Geobacillus, Lactobacillus,Lactococcus, Oceanobacillus, Staphylococcus, Streptococcus, andStreptomyces. Gram-negative bacteria include, but are not limited to,Campylobacter, E. coli, Flavobacterium, Fusobacterium, Helicobacter,ilyobacter, Neisseria, Pseudomonas, Salmonella, and Ureaplasma.

Methods according to the Invention

The present invention also relates to methods of producing a variant,comprising: (a) cultivating a host cell of the present invention underconditions suitable for expression of the variant; and (b) recoveringthe variant. Thus, the present invention relates to a method ofproducing a variant comprising an alteration in one or more positionscorresponding to the positions H1, T5, G7, Q11, N16, V17, Q32, A37, T40,P45, W48, G50, T51, N54, V56, K72, R87, Q98, M105, G109, F113, R116,Q118, Q125, G133, T134, W140, G142, G149, T165, W167, Q169, R171, Q172,L173, A174, G184, A186, E190, T193, N195, A204, V206, P211, I214, V215,L217, L219, A225, L235, V238, K242, S244, M246, M248, L250, G255, Q256,N260, A263, V264, Y267, K269, N270, G273, S280, W284, T285, M286, F289,V291, Y295, Q299, R320, H321, S323, H324, V326, F328, T334, D337, Q345,G346, G348, T355, S376, D377, D379, Y382, S383, Q385, K391, K393, Q395,A420, G423, T444, A445, Q449, T459, P473, C474, G476, G477, and K484 ofSEQ ID NO: 13; or H1, A37, T40, N54, V56, A60, K72, G109, F113, P116,N125, F133, T134, T165, Q169, Q172, L173, A174, G184, A186, E190, N195,G196, A204, V206, A225, L228, K242, S244, G255, N260, A265, K269, S280,W284, Y295, S304, R320, H321, S323, V326, K391, I405, A421, A422, A428,R439, G448, W467, D476, and G477 of SEQ ID NO: 14, wherein the methodcomprises the steps of a) cultivating a host cell according to theinvention under conditions suitable for expression of the variant, andb) recovering the variant.

The host cells are cultivated in a nutrient medium suitable forproduction of the variant using methods known in the art. For example,the cell may be cultivated by shake flask cultivation, or small-scale orlarge-scale fermentation (including continuous, batch, fed-batch, orsolid state fermentations) in laboratory or industrial fermentorsperformed in a suitable medium and under conditions allowing the variantto be expressed and/or isolated. The cultivation takes place in asuitable nutrient medium comprising carbon and nitrogen sources andinorganic salts, using procedures known in the art. Suitable media areavailable from commercial suppliers or may be prepared according topublished compositions (e.g., in catalogues of the American Type CultureCollection), If the variant is secreted into the nutrient medium, thevariant can be recovered directly from the medium. If the variant is notsecreted, it can be recovered from cell lysates.

The variant may be detected using methods known in the art that arespecific for the polypeptides having alpha amylase activity. Thesedetection methods include, but are not limited to, use of specificantibodies, formation of an enzyme product, or disappearance of anenzyme substrate. For example, an enzyme assay may be used to determinethe activity of the variant.

The variant may be recovered using methods known in the art. Forexample, the variant may be recovered from the nutrient medium byconventional procedures including, but not limited to, collection,centrifugation, filtration, extraction, spray-drying, evaporation, orprecipitation.

The variant may be purified by a variety of procedures known in the artincluding, but not limited to, chromatography (e.g., ion exchange,affinity, hydrophobic, chromatofocusing, and size exclusion),electrophoretic procedures (e.g., preparative isoelectric focusing),differential solubility (e.g.; ammonium sulfate precipitation),SDS-PAGE, or extraction (see, e.g., Protein Purification, Janson andRyden, editors, VCH Publishers, New York, 1989) to obtain substantiallypure variants.

In an alternative aspect, the variant is not recovered, but rather ahost cell of the present invention expressing the variant is used as asource of the variant.

Furthermore, the present invention relates to methods for obtaining avariant, comprising introducing into a parent alpha-amylase having atleast 80% sequence identity to the polypeptide of SEQ ID NO: 4

-   -   (a) a substitution and/or deletion of two or more positions in        the parent alpha-amylase said positions corresponding to        positions 181, 182, 183, and 184 of the mature polypeptide of        SEQ ID NO: 4; and    -   (b) an alteration at one or more positions corresponding to        positions H1, T5, G7, Q11, N16, V17, Q32, A37, T40, P45, W48,        G50, T51, N54, V56, K72, R87, Q98, M105, G109, F113, R116, Q118,        Q125, G133, T134, W140, G142, G149, T165, W167, Q169, R171,        Q172, L173, A174, G184, A186, E190, T193, N195, A204, V206,        P211, I214, V215, L217, L219, A225, L235, V238, K242, S244,        M246, M248, L250, G255, Q256, N260, A263, V264, Y267, K269,        N270, G273, S280, W284, T285, M286, F289, V291, Y295, Q299,        R320, H321, S323, H324, V326, F328, T334, D337, Q345, G346,        G348, T355, S376, D377, D379, Y382, S383, Q385, K391, K393,        Q395, A420, G423, T444, A445, Q449, T459, P473, C474, G476,        G477, and K484 of SEQ ID NO: 13; or H1, A37, T40, N54, V56, A60,        K72, G109, F113, R116, N125, F133, T134, T165, Q169, Q172, L173,        A174, G184, A186, E190, N195, G196, A204, V206, A225, L228,        K242, S244, G255, N260, A265, K269, S280, W284, Y295, S304,        R320, H321, S323, V326, K391, I405, A421, A422, A428, R439,        G448, W467, D476, and G477 of SEQ ID NO: 14,    -   wherein the resulting variant has at least 80%, such as at least        85%, such as at least 90%, such as at least 95%, such as at        least 97%, but less than 100% sequence identity with the mature        polypeptide of SEQ ID NO: 4, wherein said variant has        alpha-amylase activity;

(c) recovering said variant.

The variants may be prepared using any mutagenesis procedure known inthe art, such as site-directed mutagenesis, synthetic gene construction,semi-synthetic gene construction, random mutagenesis, shuffling, etc.

Site-directed mutagenesis is a technique in which one or more (e.g.,several) mutations are introduced at one or more defined sites in apolynucleotide encoding the parent.

Site-directed mutagenesis can be accomplished in vitro by PCR involvingthe use of oligonucleotide primers containing the desired mutation.Site-directed mutagenesis can also be performed in vitro by cassettemutagenesis involving the cleavage by a restriction enzyme at a site inthe plasmid comprising a polynucleotide encoding the parent polypeptideand subsequent ligation of an oligonucleotide containing the mutation inthe polynucleotide. Usually the restriction enzyme that digests theplasmid and the oligonucleotide is the same, permitting sticky ends ofthe plasmid and the insert to ligate to one another. See, e.g., Schererand Davis, 1979, Proc. Natl. Acad. Sci. USA 76: 4949-4955; and Barton etal., 1990, Nucleic Acids Res. 18: 7349-4966.

Site-directed mutagenesis can also be accomplished in vivo by methodsknown in the art. See, e.g., U.S. Patent Application Publication No.2004/0171154; Storici et al., 2001, Nature Biotechnol. 19: 773-776; Krenet al., 1998, Nat. Med. 4: 285-290; and Calissano and Macino, 1996,Fungal Genet, Newslett. 43: 15-16.

Any site-directed mutagenesis procedure may be used in the presentinvention. There are many commercial kits available that can be used toprepare variants. The skilled person in the art is well-aware of suchcommercial kits and how to use them.

Synthetic gene construction entails in vitro synthesis of a designedpolynucleotide molecule to encode a polypeptide of interest, Genesynthesis may be performed utilizing a number of techniques, such as themultiplex microchip-based technology described by Tian et al. (2004.Nature 432: 1050-1054) and similar technologies wherein oligonucleotidesare synthesized and assembled upon photo-programmable microfluidicchips.

Single or multiple amino acid substitutions, deletions, and/orinsertions may be made and tested using known methods of mutagenesis,recombination, and/or shuffling, followed by a relevant screeningprocedure, such as those disclosed by Reidhaar-Olson and Sauer, 1988,Science 241: 53-57; Bowie and Sauer, 1989, Proc, Natl, Acad. Sci. USA86: 2152-2156; WO 95/17413; or WO 95/22625. Other methods that may beused include error-prone FOR, phage display (e.g., Lowman et al., 1991,Biochemistry 30: 10832-10837; U.S. Pat. No. 5,223,409; WO 92/06204) andregion-directed mutagenesis (Derbyshire et al., 1986, Gene 46: 145; Neret al., 1988. DNA 7: 127).

Mutagenesis/shuffling methods may be combined with high-throughput,automated screening methods to detect activity of cloned, mutagenizedpolypeptides expressed by host cells (Ness et al., 1999, NatureBiotechnology 17: 893-896), Mutagenized DNA molecules that encode activepolypeptides may be recovered from the host cells and rapidly sequencedusing standard methods in the art. These methods allow the rapiddetermination of the importance of individual amino acid residues in apolypeptide.

Semi-synthetic gene construction is accomplished by combining aspects ofsynthetic gene construction, and/or site-directed mutagenesis, and/orrandom mutagenesis, and/or shuffling. Semi-synthetic construction istypified by a process utilizing polynucleotide fragments that aresynthesized, in combination with PCR techniques. Defined regions ofgenes may thus be synthesized de novo, while other regions may beamplified using site-specific mutagenic primers, while yet other regionsmay be subjected to error-prone PCR or non-error prone PCRamplification. Polynucleotide subsequences may then be shuffled.

The present invention also relates to a method of improving washperformance of a parent polypeptide having the amino acid sequence ofSEQ ID NO: 13 or 14, or having at least 80% sequence identity thereto,said method comprising the steps of:

-   -   a) a substitution and/or deletion of two, three or four        positions in the parent alpha-amylase said positions        corresponding to positions 181, G182, D183, and G184 of the        mature polypeptide of SEQ ID NO: 4; and    -   b) an alteration at one or more positions corresponding to        positions H1, T5, G7, Q11, N16, V17, Q32, A37, T40, P45, W48,        G50, T51, N54, V56, K72, R87, Q98, M105, G109, F113, R116, Q118,        Q125, G133, T134, W140, G142, G149, T165, W167, Q169, R171,        Q172, L173, A174, G184, A186, E190, T193, N195, A204, V206,        P211, I214, V215, L217, L219, A225, L235, V238, K242, S244,        M246, M248, L250, G255, Q256, N260, A263, V264, Y267, K269,        N270, G273, S280, W284, T285, M286, F289, V291, Y295, Q299,        R320, H321, S323, H324, V326, F328, T334, D337, Q345, G346,        G348, T355, S376, D377, D379, Y382, S383, Q385, K391, K393,        Q395, A420, G423, T444, A445, Q449, T459, P473, C474, G476,        G477, and K484 of SEQ ID NO: 13; or H1, A37, T40, N54, V56, A60,        K72, G109, F113, R116, N125, F133, T134, T165, Q169, Q172, L173,        A174, G184, A186, E190, N195, G196, A204, V206, A225, L228,        K242, S244, G255, N260, A265, K269, S280, W284, Y295, S304,        R320, H321, S323, V326, K391, I405, A421, A422, A428, R439,        G448, W467, D476, and G477 of SEQ ID NO: 14,    -   wherein the variant has at least 80%, at least 85%, at least        90%, at least 95%, at least 97%, at least 98%, at least 99%, but        less than 100% sequence identity with the polypeptide of SEQ ID        NO: 4 or 7, and wherein the variant has alpha-amylase activity        and improved wash performance compared to the parent        polypeptide.

In one embodiment, the variant has at least 50%, such as at least 60%,or at least 70%, or at least 80%, or at least 90%, or at least 100% ofthe activity of the parent polypeptide having the amino acid sequence ofSEQ ID NO: 7.

In one embodiment, the activity is determined according to a Phadebasassay.

The alpha-amylase activity may be determined by a method using thePhadebas substrate (from for example Magle Life Sciences, Lund, Sweden).A Phadebas tablet includes interlinked starch polymers that are in theform of globular microspheres that are insoluble in water. A blue dye iscovalently bound to these microspheres. The interlinked starch polymersin the microsphere are degraded at a speed that is proportional to thealpha-amylase activity. When the alpha-amylase degrades the starchpolymers, the released blue dye is water soluble and concentration ofdye can be determined by measuring absorbance at 620 nm. Theconcentration of blue is proportional to the alpha-amylase activity inthe sample.

The variant sample to be analyzed is diluted in activity buffer with thedesired pH. Two substrate tablets are suspended in 5 mL activity bufferand mixed on magnetic stirrer. During mixing of substrate transfer 150μl to microtiter plate (MTP) or PCR-MTP, Add 30 μl diluted amylasesample to 150 μl substrate and mix. Incubate for 15 minutes at 37° C.The reaction is stopped by adding 30 μl 1M NaOH and mix. Centrifuge MTPfor 5 minutes at 4000×g. Transfer 100 μl to new MTP and measureabsorbance at 620 nm.

The alpha-amylase sample should be diluted so that the absorbance at 620nm is between 0 and 2.2, and is within the linear range of the activityassay.

Thus, in one embodiment, the activity is determined by by a methodcomprising the steps of;

-   -   a) incubating an alpha-amylase variant according to the        invention with a dyed amylose substrate for 15 minute at 37° C.:        and    -   b) measuring the absorption at OD 620 nm.

In a further embodiment, the activity is determined by a methodcomprising the steps of;

-   -   a) incubating an alpha-amylase variant according to the        invention with a dyed amylose substrate for 15 minute at 37° C.:        and    -   b) centrifuging the sample;    -   c) transferring the supernatant to reader plate, and measuring        the absorption at OD 620 nm,

Fermentation Broth Formulations or Cell Compositions

The present invention also relates to a fermentation broth formulationor a cell composition comprising a polypeptide of the present invention.Thus, in one embodiment, the fermentation broth formulation or the cellcomposition comprises a polynucleotide encoding a variant comprising analteration in one or more positions corresponding to the positions H1,T5, G7, Q11, N16, V17, Q32, A37, T40, P45, W48, G50, T51, N54, V56, K72,R87, Q98, M105, G109, F113, R116, Q118, Q125, G133, T134, W140, G142,G149, T165, W167, Q169, R171, Q172, L173, A174, G184, A186, E190, T193,N195, A204, V206, P211, I214, V215, L217, L219, A225, L235, V238, K242,S244, M246, M248, L250, G255, Q256, N260, A263, V264, Y267. K269, N270,G273, S280, W284, T285, M286, F289, V291, Y295, Q299, R320, H321, S323,H324, V326, F328, T334, D337, Q345, G346, G348, T355, S376, D377, D379,Y382, S383, Q385, K391, K393, Q395, A420, G423, T444, A445, Q449, T459,P473, C474, G476, G477, and K484 of SEQ ID NO: 13, or H1, A37, T40, N54,V56, A60, K72, G109, F113, R116, N125, F133, T134, T165, Q169, Q172,L173, A174, G184, A186, E190, N195, G196, A204, V206, A225, L228, I242,S244, G255, N260, A265, K269, S280, W284, Y295, R304, R320, H321, S323,V326, K391, I405, A421, A422, A428, R439, G448, W467, D476, and G477 ofSEQ ID NO: 14, a nucleic acid construct encoding a variant comprising analteration in one or more positions corresponding to the positions H1,T5, G7, Q11, N16, V17, Q32, A37, T40, P45, W48, G50, T51, N54, V56, K72,R87, Q98, M105, G109, F113, R116, Q118, Q125, G133, T134, W140, G142,G149, T165, W167, Q169, R171, Q172, L173, A174, G184, A186, E190, T193,N195, A204, V206, P211, I214, V215, L217, L219, A225, L235, V238, K242,S244, M246, M248, L250, G255, Q256, N260, A263, V264, Y267, K269, N270,G273, S280, W284, T285, M286, F289, V291, Y295, Q299, R320, H321, S323,H324, V326, F328, T334, D337, Q345, G346, G348, T355, S376, D377, D379,Y382, S383, Q385, K391, K393, Q395, A420, G423, T444, A445, Q449, T459,P473, C474, G476, G477, and K484 of SEQ ID NO: 13; or H1, A37, T40, N54,V56, A60, K72, G109, F113, R116, N125, F133, T134, T165, Q169, Q172,L173, A174, G184, A186, E190, N195, G196, A204, V206, A225, L228, K242,S244, G255, N260, A265, K269, S280, W284, Y295, S304, R320, H321, S323,V326, K391, I405, A421, A422, A428, R439, G448, W467, D476, and G477 ofSEQ ID NO: 14, or an expression vector encoding a variant comprising analteration in one or more positions corresponding to the positions H1,T5, G7, Q11, N16, V17, Q32, A37, T40, P45, W48, G50, T51, N54, V56, K72,R87, Q98, M105, G109, F113, R116, Q118, Q125, G133, T134, W140, G142,G149, T165, W167, Q269, R171, Q172, L173, A174, G184, A186, E190, T193,N195, A204, V206, P211, I214, V215, L217, L219, A225, L235, V238, K242,S244, M246, M248, L250, G255, Q256, N260, A263, V264, Y267, K269, N270,G273, R280, W284, T285, M286, F289, V291, Y295, Q299, R320, H321, S323,H324, V326, F328, T334, D337, Q345, G346, G348, T355, S376, D377, D379,Y382, S383, Q385, K391, K393, Q395, A420, G423, T444, A445, Q449, T459,P473, C474, G476, G477, and K484 of SEQ ID NO: 13; or H1, A37, T40, N54,V56, A60, K72, G109, F113, R116, N125, F133, T134, T165, Q169, Q172,L173, A174, G184, A186, E190, N195, G196, A204, V206, A225, L228, K242,S244, G255, N260, A265, K269, S280, W284, Y295, S304, R320, H321, S323,V326, K391, I405, A421, A422, A428, R439, G448, W467, D476, and G477 ofSEQ ID NO: 14. The fermentation broth product may further compriseadditional ingredients used in the fermentation process, such as, forexample, cells (including, the host cells containing the gene encodingthe polypeptide of the present Invention which are used to produce thepolypeptide of interest), cell debris, biomass, fermentation mediaand/or fermentation products. In some embodiments, the composition is acell-Filled whole broth containing organic acid(s), killed cells and/orcell debris, and culture medium.

The term “fermentation broth” as used herein refers to a preparationproduced by cellular fermentation that undergoes no or minimal recoveryand/or purification. For example, fermentation broths are produced whenmicrobial cultures are grown to saturation, incubated undercarbon-limiting conditions to allow protein synthesis (e.g., expressionof enzymes by host cells) and secretion into cell culture medium. Thefermentation broth can contain unfractionated or fractionated contentsof the fermentation materials derived at the end of the fermentation,Typically, the fermentation broth is unfractionated and comprises thespent culture medium and cell debris present after the microbial cells(e.g., filamentous fungal cells) are removed, e.g., by centrifugation.In some embodiments, the fermentation broth contains spent cell culturemedium, extracellular enzymes, and viable and/or nonviable microbialcells.

In one embodiment, the fermentation broth formulation and cellcompositions comprise a first organic acid component comprising at leastone 1-5 carbon organic acid and/or a salt thereof and a second organicacid component comprising at least one 6 or more carbon organic acidand/or a salt thereof. In a particular embodiment, the first organicacid component is acetic acid, formic acid, propionic acid, a saltthereof, or a mixture of two or more of the foregoing and the secondorganic acid component is benzoic acid, cyclohexanecarboxylic acid,4-methylvaleric acid, phenylacetic acid, a salt thereof, or a mixture oftwo or more of the foregoing.

In one embodiment, the composition contains an organic acid(s), andoptionally further contains killed cells and/or cell debris. In oneembodiment, the killed cells and/or cell debris are removed from acell-killed whole broth to provide a composition that is free of thesecomponents.

The fermentation broth formulations or cell compositions may furthercomprise a preservative and/or anti-microbial (e.g., bacteriostatic)agent, including, but not limited to, sorbitol, sodium chloride,potassium sorbate, and others known in the art.

The cell-killed whole broth or composition may comprise theunfractionated contents of the fermentation materials derived at the endof the fermentation. Typically, the cell-killed whole broth orcomposition comprises the spent culture medium and cell debris presentafter the microbial cells (e.g., filamentous fungal cells) are grown tosaturation, incubated under carbon-limiting conditions to allow proteinsynthesis. In some embodiments, the cell-killed whole broth orcomposition comprises the spent cell culture medium, extracellularenzymes, and killed filamentous fungal cells. In some embodiments, themicrobial cells present in the cell-killed whole broth or compositionmay be permeabilized and/or lysed using methods known in the art.

A whole broth or cell composition as described herein is typically aliquid, but may comprise insoluble components, such as killed cells,cell debris, culture media components, and/or insoluble enzyme(s). Insome embodiments, insoluble components may be removed to provide aclarified liquid composition.

The whole broth formulations and cell compositions of the presentinvention may be produced by a method described in WO 90/15861 or WO2010/096673,

Enzyme Compositions

The present invention also relates to compositions comprising a variantaccording to the invention. Thus, the invention relates to a compositioncomprising a variant comprising an alteration in one or more positionscorresponding to the positions 1-11, T5, G7, Q11, N16, V17, Q32, A37,T40, P45, W48, G50, T51, N54, V56, K72, R87, Q98, M105, G109, F113,R116, Q118, Q125, G133, T134, W140, G142, G149, T165, W167, Q169, R171,Q172, L173, A174, G184, A186, E190, T193, N195, A204, V206, P211, I214,V215, L217, L219, A225, L235, V238, K242, S244, M246, M248, L250, G255,Q256, N260, A263, V264, Y267, K269, N270, G273, S280, W284, T285, M286,F289, V291, Y295, Q299, R320, H321, S323, H324, V326, F328, T334, D337,Q345, G346, G348, T355, S376, D377, D379, Y382, S383, Q385, K391, K393,Q395, A420, G423, T444, A445, Q449, T459, P473, C474, G476. G477, andK484 of SEQ ID NO: 13; or H1, A37, T40, N54, V56, A60, K72, G109, F113,R116, N125, F133, T134, T165, Q169, Q172, L173, A174, G184, A186, E190,N195, G196, A204, V206, A225, L228, K242, S244, G255, N260, A265, K269,S280, W284, Y295, S304, R320, H321, S323, V326, K391, I405, A421, A422,A428, R439, G448, W467, D476, and G477 of SEQ ID NO: 14.

In one embodiment, the composition comprises a variant comprising

-   -   a) a deletion and/or a substitution at two or more positions        corresponding to positions R181. G182, D183, and G184 of the        amino acid sequence as set forth in SEQ ID NOs; 7 or 10, and    -   b) an alteration at one or more positions corresponding to        positions H1, T5, G7, Q11, N16, V17, Q32, A37, T40, P45, W48,        G50, T51, N54, V56, K72, R87, Q98, M105, G109, F113, R116, Q118,        Q125, G133, T134, W140, G142, G149, T165, W167, Q169, R171,        Q172, T173, A174, A186, E190, T193, N195, A204, V206, P211,        V213, I214. L217, A225, L235, V238, K242, S244, M246, L250,        G255, Q256, N260, A263, V264, Y267, K269, N270, G273, R280,        W284, T285, M286, F289, V291, Y295, Q299, R320, H321, S323,        H324, V326, F328, T334, G337, Q345, G346, T355, R376, D377,        S381, Y382, Q385, K391, K393, Q395, A420, G423, T444, A445,        Q449, T459, P473, C474, G476, G477, and K484 of SEQ ID NO: 13;        or H1, A37, T40, N54, V56, A60, K72, G109, F113, R116, N125,        F133, T134, T165, Q169, Q172, L173, A174, G184, A186, E190,        N195, G196, A204, V206, A225, L228, K242, S244, G255, N260,        A265, K269, S280, W284, Y295, S304, R320, H321, R323, V326,        K391, I405, A421, A422, A428, R439, G448, W467, D476, and G477        of SEQ ID NO: 14. Preferably, the compositions are enriched in        such a variant. The term “enriched” as used herein, refers to        that the alpha-amylase activity of the composition has been        increased, e.g., with an enrichment factor of at least 1.1.

The compositions may comprise a variant of the present invention as themajor enzymatic component, e.g., a mono-component composition. Inanother embodiment, the composition further comprises at least onefurther active component.

The term “active component” as used herein, refers to any biological ornon-biological molecule which in itself is active. For example, anactive component is an enzyme.

Thus, in one embodiment, the further active component is an enzyme, suchas a protease, lipase, cellulose, pectate lyase and mannanase. Thus, thecompositions may comprise multiple enzymatic activities, such as one ormore (e.g., several) enzymes selected from the group consisting ofhydrolase, isomerase, ligase, lyase, oxidoreductase, or transferase,e.g., an alpha-galactosidase, alpha-glucosidase, aminopeptidase,amylase, beta-galactosidase, beta-glucosidase, beta-xylosidase,carbohydrase, carboxypeptidase, catalase, cellobiohydrolase, cellulase,chitinase, cutinase, cyclodextrin glycosyltransferase,deoxyribonuclease, endoglucanase, esterase, glucoamylase, invertase,laccase, lipase, mannosidase, mutanase, oxidase, pectinolytic enzyme,peroxidase, phytase, polyphenoloxidase, proteolytic enzyme,ribonuclease, transglutaminase, or xylanase.

In one embodiment, the composition is a liquid laundry or liquid dishwash composition, such as an Automatic Dish Wash (ADW) liquid detergentcomposition, or a powder laundry, such as a soap bar, or powder dishwash composition, such as an ADW unit dose detergent composition andsuch as a Hand Dish Wash (HDW) detergent composition.

The choice of additional components is within the skills of the skilledperson in the art and includes conventional ingredients, including theexemplary non-limiting components set forth below. The choice ofcomponents may include, for fabric care, the consideration of the typeof fabric to be cleaned, the type and/or degree of soiling, thetemperature at which cleaning is to take place, and the formulation ofthe detergent product. Although components mentioned below arecategorized by general header according to a particular functionality,this is not to be construed as a limitation, as a component may compriseadditional functionalities as will be appreciated by the skilledartisan.

In one embodiment of the present invention, the variant of the presentinvention may be added to a detergent composition in an amountcorresponding to 0.001-100 mg of protein, such as 0.01-100 mg ofprotein, preferably 0.005-50 mg of protein, more preferably 0.01-25 mgof protein, even more preferably 0.05-10 mg of protein, most preferably0.05-5 mg of protein, and even most preferably 0.01-1 mg of protein perliter of wash liquor. The term “protein” in this context is contemplatedto be understood to include a variant according to the presentinvention.

A composition for use in automatic dish wash (ADW), for example, mayinclude 0.0001%-50%, such as 0.001%-20%, such as 0.01%-10%, such as0.05-5% of enzyme protein by weight of the composition.

A composition for use in laundry granulation, for example, may include0.0001%-50%, such as 0.001%-20%, such as 0.01%-10%, such as 0.05%-5% ofenzyme protein by weight of the composition.

A composition for use in laundry liquid, for example, may include0.0001%-10%, such as 0.001-7%, such as 0.1%-5% of enzyme protein byweight of the composition.

The variants of the invention as well as the further active components,such as additional enzymes, may be stabilized using conventionalstabilizing agents, e.g., a polyol such as propylene glycol or glycerol,a sugar or sugar alcohol, lactic acid, boric acid, or a boric acidderivative, e.g., an aromatic borate ester, or a phenyl boronic acidderivative such as 4-formylphenyl boronic acid, and the composition maybe formulated as described in, for example, WO92/19709 and WO92/19708.

In certain markets different wash conditions and, as such, differenttypes of detergents are used. This is disclosed in e.g. EP 1 025 240.For example, In Asia (Japan) a low detergent concentration system isused, while the United States uses a medium detergent concentrationsystem, and Europe uses a high detergent concentration system.

A low detergent concentration system includes detergents where less thanabout 800 ppm of detergent components are present in the wash water.Japanese detergents are typically considered low detergent concentrationsystem as they have approximately 667 ppm of detergent componentspresent in the wash water.

A medium detergent concentration includes detergents where between about800 ppm and about 2000 ppm of detergent components are present in thewash water. North American detergents are generally considered to bemedium detergent concentration systems as they have approximately 975ppm of detergent components present in the wash water.

A high detergent concentration system includes detergents where greaterthan about 2000 ppm of detergent components are present in the washwater. European detergents are generally considered to be high detergentconcentration systems as they have approximately 4500-5000 ppm ofdetergent components in the wash water.

Latin American detergents are generally high suds phosphate builderdetergents and the range of detergents used in Latin America can fall inboth the medium and high detergent concentrations as they range from1500 ppm to 6000 ppm of detergent components in the wash water. Suchdetergent compositions are all embodiments of the invention.

A variant of the present invention may also be incorporated in thedetergent formulations disclosed in WO97/07202, which is herebyincorporated by reference.

Examples are given herein of preferred uses of the compositions of thepresent invention. The dosage of the composition and other conditionsunder which the composition is used may be determined on the basis ofmethods known in the art.

In particular, a composition according to the present invention furthercomprises a chelator.

The term “chelator” as used herein, refers to chemicals which formmolecules with certain metal ions, inactivating the ions so that theycannot react with other elements. Thus, a chelator may be defined as abinding agent that suppresses chemical activity by forming chelates.

Chelation is the formation or presence of two or more separate bindingsbetween a ligand and a single central atom. The ligand may be anyorganic compound, a silicate or a phosphate. In the present context theterm “chelating agents” comprises chelants, chelating agent, chelatingagents, complexing agents, or sequestering agents that formswater-soluble complexes with metal ions such as calcium and magnesium.The chelate effect describes the enhanced affinity of chelating ligandsfor a metal ion compared to the affinity of a collection of similarnonchelating ligands for the same metal. Chelating agents having bindingcapacity with metal ions, in particular calcium (Ca2+) ions, and hasbeen used widely in detergents and compositions in general for wash,such as laundry or dish wash. Chelating agents have however shownthemselves to inhibit enzymatic activity. The term chelating agent isused in the present application interchangeably with “complexing agent”or “chelating agent” or “chelant”.

Since most alpha-amylases are calcium sensitive the presence ofchelating agents these may impair the enzyme activity. The calciumsensitivity of alpha-amylases can be determined by incubating a givenalpha-amylase in the presence of a strong chelating agent and analyzethe impact of this incubation on the activity of the alpha-amylase inquestion. A calcium sensitive alpha-amylase will lose a major part orall of its activity during the incubation. Chelating agent may bepresent in the composition in an amount from 0.0001 wt % to 20 wt %,preferably from 0.01 to 10 wt %, more preferably from 0.1 to 5 wt %.

Non-limiting examples of chelating agents are; EDTA, DTMPA, HEDP, andcitrate. Thus, in one embodiment, the composition comprises a variantaccording to the invention and a chelating agent, such as EDTA, DTMPA,HEDP or citrate.

The term “EDTA” as used herein, refers to ethylene-diamine-tetra-aceticacid which falls under the definition of “strong chelating agents”.

The term “DTMPA” as used herein, refers to diethylenetriaminepenta(methylene phosphonic acid). DTMPA can inhibit the scale formationof carbonate, sulfate and phosphate.

The term “HEDP” as used herein, refers to hydroxy-ethane diphosphonicacid, which falls under the definition of “strong chelating agents”.

The chelate effect or the chelating effect describes the enhancedaffinity of chelating ligands for a metal ion compared to the affinityof a collection of similar nonchelating ligands for the same metal.However, the strength of this chelate effect can be determined byvarious types of assays or measure methods thereby differentiating orranking the chelating agents according to their chelating effect (orstrength).

In an assay the chelating agents may be characterized by their abilityto reduce the concentration of free calcium ions (Ca2+) from 2.0 mM to0.10 mM or less at pH 8.0, e.g. by using a test based on the methoddescribed by M. K. Nagarajan et al., JAOCS, Vol. 61, no. 9 (September1984), pp. 1475-1478.

For reference, a chelator having the same ability to reduce theconcentration of free calcium ions (Ca2+) from 2.0 mM to 0.10 mM at pHas EDTA at equal concentrations of the chelator are said to be strongchelators.

The composition of the present invention may be in any convenient form,e.g., a bar, a homogenous tablet, a tablet having two or more layers, apouch having one or more compartments, a regular or compact powder, agranule, a paste, a gel, or a regular, compact or concentrated liquid.There are a number of detergent formulation forms such as layers (sameor different phases), pouches, as well as forms for machine dosing unit.

Pouches can be configured as single or multicompartments. It can be ofany form, shape and material which is suitable for hold the composition,e.g. without allowing the release of the composition from the pouchprior to water contact. The pouch is made from water soluble film whichencloses an inner volume. Said inner volume can be divided intocompartments of the pouch. Preferred films are polymeric materialspreferably polymers which are formed into a film or sheet. Preferredpolymers, copolymers or derivatives thereof are selected polyacrylates,and water soluble acrylate copolymers, methyl cellulose, carboxy methylcellulose, sodium dextrin, ethyl cellulose, hydroxyethyl cellulose,hydroxypropyl methyl cellulose, malto dextrin, poly methacrylates, mostpreferably polyvinyl alcohol copolymers and, hydroxypropyl methylcellulose (HPMC). Preferably the level of polymer in the film forexample PVA is at least about 60%. Preferred average molecular weightwill typically be about 20,000 to about 150,000. Films can also be ofblend compositions comprising hydrolytically degradable and watersoluble polymer blends such as polyactide and polyvinyl alcohol (knownunder the Trade reference M8630 as sold by Chris Craft In. Prod, OfGary, Ind., US) plus plasticisers like glycerol, ethylene glycerol,Propylene glycol, sorbitol and mixtures thereof. The pouches cancomprise a solid laundry cleaning composition or part components and/ora liquid cleaning composition or part components separated by the watersoluble film. The compartment for liquid components can be different incomposition than compartments containing solids. Ref: (US2009/0011970A1).

Detergent ingredients may be separated physically from each other bycompartments in water dissolvable pouches or in different layers oftablets. Thereby negative storage interaction between components may beavoided. Different dissolution profiles of each of the compartments canalso give rise to delayed dissolution of selected components in the washsolution.

A liquid or gel detergent, which is not unit dosed, may be aqueous,typically containing at least 20% by weight and up to 95% water, such asup to about 70% water, up to about 65% water, up to about 55% water, upto about 45% water, up to about 35% water. Other types of liquids,including without limitation, alkanols, amines, dials, ethers andpolyols may be included in an aqueous liquid or gel. An aqueous liquidor gel detergent may contain from 0-30% organic solvent. A liquid or geldetergent may be non-aqueous.

Another form of composition is in the form of a soap bar, such as alaundry soap bar, and may be used for hand washing laundry, fabricsand/or textiles. The term “soap bar” as used herein, refers to includeslaundry bars, soap bars, combo bars, syndet bars and detergent bars. Thetypes of bar usually differ in the type of surfactant they contain, andthe term laundry soap bar includes those containing soaps from fattyacids and/or synthetic soaps. The laundry soap bar has a physical formwhich is solid and not a liquid, gel or a powder at room temperature.The term “solid” as used herein, refers to a physical form which doesnot significantly change over time, i.e. if a solid object (e.g. laundrysoap bar) is placed inside a container, the solid object does not changeto fill the container it is placed in. The bar is a solid typically inbar form but can be in other solid shapes such as round or oval.

The soap bar may also comprise complexing agents like EDTA and HEDP,perfumes and/or different type of fillers, surfactants e.g. anionicsynthetic surfactants, builders, polymeric soil release agents,detergent chelators, stabilizing agents, fillers, dyes, colorants, dyetransfer inhibitors, alkoxylated polycarbonates, suds suppressers,structurants, binders, leaching agents, bleaching activators, clay soilremoval agents, anti-redeposition agents, polymeric dispersing agents,brighteners, fabric softeners, perfumes and/or other compounds known inthe art.

The soap bar may be processed in conventional laundry soap bar makingequipment such as but not limited to: mixers, plodders, e.g. a two stagevacuum plodder, extruders, cutters, logo-stampers, cooling tunnels andwrappers. The invention is not limited to preparing the soap bars by anysingle method. The premix of the invention may be added to the soap atdifferent stages of the process. For example, the premix comprising asoap, an enzyme, optionally one or more additional enzymes, a proteaseinhibitor, and a salt of a monovalent cation and an organic anion may beprepared and the mixture may then plodded. The enzyme and optionaladditional enzymes may be added at the same time as an enzyme inhibitor,e.g. a protease inhibitor, for example in liquid form. Besides themixing step and the plodding step, the process may further comprise thesteps of milling, extruding, cutting, stamping, cooling and/or wrapping.

Uses

The present invention further relates to the use of a variant accordingto the present invention in a cleaning process such as laundry or hardsurface cleaning including automated dish wash and industrial cleaning.The soils and stains that are important for cleaning are composed ofmany different substances, and a range of different enzymes, all withdifferent substrate specificities, have been developed for use indetergents both in relation to laundry and hard surface cleaning, suchas dishwashing. These enzymes are considered to provide an enzymedetergency benefit, since they specifically improve stain removal in thecleaning process that they are used in, compared to the same processwithout enzymes. Stain removing enzymes that are known in the artinclude enzymes such as proteases, amylases, lipases, cutinases,cellulases, endoglucanases, xyloglucanases, pectinases, pectin lyases,xanthanases, peroxidaes, haloperoxygenases, catalases and mannanases.

In one embodiment, the invention relates the use of variants of thepresent invention in detergent compositions, for use in cleaninghard-surfaces, such as dish wash, or in laundering or for stain removal.In another embodiment, the invention relates to the use of analpha-amylase variant according to the invention in a cleaning processsuch as laundry or hard surface cleaning including, but not limited to,dish wash and industrial cleaning. Thus, in one embodiment, theinvention relates to the use of a variant comprising an alteration inone or more positions corresponding to the positions H1, T5, G7, Q11,N16, V17, Q32, A37, T40, P45, W48, G50, T51, N54, V56, K72, R87, Q98,M105, G109, F113, R116, Q118, Q125, G133, T134, W140, G142, G149, T165,W167, Q169, R171, Q172, L173, A174, G184, A186, E190, T193, N195, A204,V206, P211, I214, V215, L217, L219, A225, L235, V238, K242, S244, M246,M248, L250, G255, Q256, N260, A263, V264, Y267, K269, N270, G273, S280,W284, T285, M286, F289, V291, Y295, Q299, R320, H321, S323, H324, V326,F328, T334, D337, Q345, G346, G348, T355, S376, D377, D379, Y382, S383,Q385, K391, K393, Q395, A420, G423, T444, A445, Q449, T459, P473, C474,G476, G477, and K484 of SEQ ID NO: 13; or H1, A37, T40, N54, V56, A60,K72, G109, F113, R116, N125, F133, T134, T165, Q169, Q172, L173, A174,G184, A186, E190, N195, G196, A204, V206, A225, L228, K242, S244, G255,N260, A265, K269, S280, W284, Y295, S304, R320, H321, S323, V326, K391,I405, A421, A422, A428, R439, G448, W467, D476, and G477 of SEQ ID NO:14 in a cleaning process such as laundry or hard surface cleaningincluding dish wash and industrial cleaning.

In a particular embodiment, the invention relates to the use of avariant comprising a) a substitution and/or deletion of two, three orfour positions in the parent alpha-amylase said positions correspondingto positions 181, G182, D183, and G184 of the mature polypeptide of SEQID NO: 4; and

-   -   b) an alteration at one or more positions corresponding to        positions positions H1, T5, G7, Q11, N16, V17, Q32, A37, T40,        P45, W48, G50, T51, N54, V56, K72, R87, Q98, M105, G109, F113,        R116, Q118, Q125, G133, T134, W140, G142, G149, T165, W167,        Q169, R171, Q172, L173, A174, G184, A186, E190, T193, N195,        A204, V206, P211, I214, V215, L217, L219, A225, L235, V238,        K242, S244, M246, M248, L250, G255, Q256, N260, A263, V264,        Y267, K269, N270, G273, S280, W284, T285, M286, F289, V291,        Y295, Q299, R320, H321, S323, H324, V326, F328, T334, D337,        Q345, G346, G348, T355, S376, D377, D379, Y382, S383, Q385,        K391, K393, Q395, A420, G423, T444, A445, Q449, T459, P473,        C474, G476, G477, and K484 of SEQ ID NO: 13: or H1, A37, T40,        N54, V56, A60, K72, G109, F113, R116, N125, F133, T134, T165,        Q169, Q172, L173, A174, G184, A186, E190, N195, G196, A204,        V206, A225, L228, K242, S244, G255, N260, A265, K269, S280,        W284, Y295, S304, R320, H321, S323, V326, K391, I405, A421,        A422, A428, R439, G448, W467, D476, and G477 of SEQ ID NO: 14,        in a cleaning process such as laundry or hard surface cleaning        including dish wash and industrial cleaning.

In one embodiment of the invention relates the use of a compositionaccording to the invention comprising a variant of the present inventiontogether with one or more surfactants and optionally one or moredetergent components, selected from the list comprising of hydrotropes,builders and co-builders, bleaching systems, polymers, fabric hoeingagents and adjunct materials, or any mixture thereof in detergentcompositions and in detergent applications.

A further embodiment is the use of the composition according to theinvention comprising a variant of the present invention together withone or more surfactants, and one or more additional enzymes selectedfrom the group comprising of proteases, lipases, cutinases, cellulases,endoglucanases, xyloglucanases, pectinases, pectin lyases, xanthanases,peroxidaes, haloperoxygenases, catalases and mannanases, or any mixturethereof in detergent compositions and in detergent applications.

In another aspect, the invention relates to a laundering process whichmay be for household laundering as well as industrial laundering.Furthermore, the invention relates to a process for the laundering oftextiles (e.g. fabrics, garments, cloths etc.) where the processcomprises treating the textile with a washing solution containing adetergent composition and an alpha-amylase of the present invention. Thelaundering can for example be carried out using a household or anindustrial washing machine or be carried out by hand using a detergentcomposition containing a glucoamylase of the invention.

In another aspect, the invention relates to a dish wash process whichmay be for household dish wash as well as industrial dish wash. The term“dish wash” as used herein, refers to both manual dish wash andautomated dish wash. Furthermore, the invention relates to a process forthe washing of hard surfaces (e.g. cutlery such as knives, forks,spoons; crockery such as plates, glasses, bowls; and pans) where theprocess comprises treating the hard surface with a washing solutioncontaining a detergent composition and an alpha-amylase variant of thepresent invention. The hard surface washing can for example be carriedout using a household or an industrial dishwasher or be carried out byhand using a detergent composition containing an alpha-amylase of theinvention, optionally together with one or more further enzymes selectedfrom the group comprising of proteases, amylases, lipases, cutinases,cellulases, endoglucanases, xyloglucanases, pectinases, pectin lyases,xanthanases, peroxidaes, haloperoxygenases, catalases, mannanases, orany mixture thereof.

In a further aspect, the invention relates to a method for removing astain from a surface comprising contacting the surface with acomposition comprising an alpha-amylase of the present inventiontogether with one or more surfactants and optionally one or moredetergent components selected from the list comprising of hydrotropes,builders and co-builders, bleaching systems, polymers, fabric hoeingagents and adjunct materials, or any mixture thereof in detergentcompositions and in detergent applications. A further aspect is a methodfor removing a stain from a surface comprising contacting the surfacewith a composition comprising an alpha-amylase variant of the presentinvention together with one or more surfactants, one or more additionalenzymes selected from the group comprising of proteases, lipases,cutinases, cellulases, endoglucanases, xyloglucanases, pectinases,pectin lyases, xanthanases, peroxidaes, haloperoxygenases, catalases andmannanases, or any mixture thereof in detergent compositions and indetergent applications.

The present invention is further described by the following examplesthat should not be construed as limiting the scope of the invention.

EXAMPLES Example 1a: Construction of the Parent Polypeptide as Set Forthin SEQ ID NO: 13

Construction of a hybrid between the A and B domain from a polypeptidehaving the amino acid sequence set forth SEQ ID NO: 10 (the first parentpolypeptide) and the C domain from a polypeptide having the amino acidsequence set forth SEQ ID NO: 11 (the second parent polypeptide).

Based on 3D structural alignment of the two amylases, amino acid no 1 toamino acid no 397 of the first parent polypeptide are defined as domainA and B, and amino acid 398 to amino acid no. 485 of the second parentpolypeptide are defined as the C domain. Synthetic DNA fragments codingfor part of the A domain from the first parent polypeptide and the Cdomain from the second parent polypeptide were designed and purchasedfrom an external vendor. In addition to combining fragments of the twodifferent amylases, the following stabilizing substitutions weredesigned into the synthetic amylase gene: G182* and D183*.

The new gene consisting of a gene fragment encoding the A and B domainof the first parent polypeptide and the C domain of the second parentpolypeptide coded by the synthetic gene fragments was constructed bytriple SOE (splicing by overlap extension) PCR method. The two fragmentswere assembled by splicing by overlap extension polymerase chainreaction and transformed into a competent B. subtilis host foroverexpression. The resulting amylase consisting of the A and B domainfrom the first parent polypeptide and the C domain from the secondparent polypeptide, and having the deletions of G182* and D183* is thepolypeptide as set forth in SEQ ID NO: 13.

Example 1b: Construction of the Parent Polypeptide as Set Forth in SEQID NO: 14

Construction of a hybrid between the A and B domain from a polypeptidehaving the amino acid sequence set forth SEQ ID NO: 10 (the first parentpolypeptide) and the C domain from a polypeptide having the amino acidsequence set forth SEQ ID NO: 12 (the third parent polypeptide).

Based on 3D structural alignment of the two amylases, amino acid no 1 toamino acid no 397 of the first parent polypeptide are defined as domainA and B, and amino acid 398 to amino acid no. 485 of the third parentpolypeptide are defined as the C domain. Synthetic DNA fragments codingfor part of the A domain from the first parent polypeptide and the Cdomain from the second parent polypeptide were designed and purchasedfrom an external vendor. In addition to combining fragments of the twodifferent amylases, the following stabilizing substitutions weredesigned into the synthetic amylase gene: G182* and D183*.

The new gene consisting of a gene fragment encoding the A and B domainof the first parent polypeptide and the C domain of the second parentpolypeptide coded by the synthetic gene fragments was constructed bytriple SOE (splicing by overlap extension) PCR method. A DNA fragmentwas amplified from an expression clone of the first amylase. Thefragments were finally assembled by triple SOE and the derived PCRfragment was transformed into a suitable B. subtilis host and the geneintegrated into the B. subtilis chromosome by homologous recombinationinto the pectate lyase (pel) locus. The gene coding for chloramphenicolacetyltransferase was used as maker (as described in (Diderichsen etal., 1993, Plasmid 30: 312-315), chloramphenicol resistant clones wereanalyzed by DNA sequencing to verify the correct DNA sequence of theconstruct. The resulting amylase consisting of the A and B domain fromthe first parent polypeptide and the C domain from the second parentpolypeptide, and having the deletions of G182* and D183* is thepolypeptide as set forth in SEQ ID NO: 14.

Example 2: Generation of Variants According to the Invention

The variants of the present invention have been generated bysite-directed mutagenesis. Genomic DNA prepared from the organismcontaining amylase gene at the Pel locus was used as template forgenerating the site-directed mutants.

Mutagenic forward primer and PnMi4490 (CAATCCAAGAGAACCCTGATACGGATG—SEQID NO: 16) reverse primer was used to generate a ˜3.8 kb fragment. Thisfragment was used as a megaprimer along with PnMi4491(CGGAACGCCTGGCTGACAACACG—SEQ ID NO: 17) forward primer to get 6 kbinsertion cassette. To enable integration in the Pel locus by doublecross-over upon transformation, along with the amylase and cat genes,the cassette contained upstream and downstream Pei sequences at theends, Selection was done on LB Agar containing chloramphenicol and themutation was confirmed by DNA sequencing of amylase gene.

A library of variants were generated where different combinations ofalterations in the following positions were made: H1, T5, G7. Q11, N16,V17, Q32, A37, I40, P45, W48, G50, T51, N54, V56, A60, K72, R87, Q98,M105, G109, F113, R116, Q118, Q125, G133, T134, W140, G142, G149, T165,W167, Q169, R171, Q172, L173, A174, G184, A186, E190, T193, N195, G196,A204, V206, P211, V213, I214, L217, A225, L228, L235, V238, K242, S244,M246, L2502, G255, N260, A263, V264, A265, Y267, K269. N270, G273, R280,W284, T285, M286, F289, V291, Y295, Q299, S304, R320, H321, S323, H324,V326, F328, T334, G337, Q345, G346, T355, R376, D377, D381. Y382, Q385,K391, and Q395 of SEQ ID NOs: 7 or 10: A420, G423, T444, A445, Q449,T459, P473, C474, G476, G477, and K484 of SEQ ID NO: 13; and I405, A421,A422, A428, G448, D476, and G477 of SEQ ID NO: 14.

The generated variants are listed in the following examples.

Example 3: Wash Performance of Generated Variants Using AutomaticMechanical Stress Assay (AMSA)

In order to assess the wash performance of the variants of the presentinvention in a detergent base composition, washing experiments may beperformed using Automatic Mechanical Stress Assay (AMSA). With the AMSAtest the wash performance of a large quantity of small volumeenzyme-detergent solutions can be examined. The AMSA plate has a numberof slots for test solutions and a lid firmly squeezing the textileswatch to be washed against all the slot openings. During the washingtime, the plate, test solutions, textile and lid were vigorously shakento bring the test solution in contact with the textile and applymechanical stress in a regular, periodic oscillating manner. For furtherdescription see WO 02/42740, especially the paragraph “Special methodembodiments” at page 23-24.

General Wash Performance Description

A test solution comprising water (6° dH), 0.79 g/L detergent, e.g. Modeldetergent J as described below, and the enzyme of the invention atconcentration of 0, 0.05 or 0.2 mg enzyme protein/L, is prepared.Fabrics stained with starch (CS-28 from Center For Test materials BY,P.O. Box 120, 3133 KT, Vlaardingen, The Netherlands) was added andwashed for 20 minutes at 15° C. and 30° C., or alternatively 20 minutesat 15° C. and 40° C. as specified below. After thorough rinse underrunning tap water and drying in the dark, the light intensity values ofthe stained fabrics were subsequently measured as a measure for washperformance. The test with 0 mg enzyme protein/L was used as a blank andcorresponded to the contribution from the detergent. Preferablymechanical action is applied during the wash step, e.g. in the form ofshaking, rotating or stirring the wash solution with the fabrics. TheAMSA wash performance experiments was conducted under the experimentalconditions specified below:

TABLE A Experimental condition Detergent Liquid Model detergent J (seeTable B) Detergent dosage 0.79 g/L Test solution volume 160 micro L pHAs is Wash time 20 minutes Temperature 15° C. or 30° C. Water hardness6° dH Enzyme concentration 0.2 mg enzyme protein/L and 0.05 mg enzyme intest protein/L Test material CS-28 (Rice starch cotton)

TABLE B Model detergent J Content of compound % active componentCompound (% w/w) (% w/w) LAS 5.15 5.00 linear alkylbenzene sulfonates AS5.00 4.50 alkylbenzene sulfonates AEOS 14.18 10.00 alkyl ethoxy sulfateCoco fatty acid 1.00 1.00 AEO 5.00 5.00 alkyl ethoxylate MEA 0.30 0.30monoethanolamine MPG 3.00 3.00 monopropylene glycol Ethanol 1.50 1.35DTPA (as Na5 salt) 0.25 0.10 pentasodium diethylenetriaminepenta- aceticacid Sodium citrate 4.00 4.00 Sodium formate 1.00 1.00 Sodium hydroxide0.66 0.66 H₂O, ion exchanged 58.95 58.95Water hardness was adjusted to 6° dH by addition of CaCl₂), MgCi₂, andNaHCO₂, (Ca²⁺:Mg²⁺:HCO₃₊=2:1:4.5) to the test system. After washing thetextiles were flushed in tap water and dried.

TABLE C Experimental condition Detergent Liquid Model detergent A (seeTable D) Detergent dosage 3.33 g/L Test solution volume 160 micro L pHAs is Wash time 20 minutes Temperature 15° C. or 40° C. Water hardness15° dH Enzyme concentration 0.2 mg enzyme protein/L, 0.05 mg enzyme intest protein/L Test material CS-28 (Rice starch cotton)

TABLE D Model detergent A Content of compound % active componentCompound (% w/w) (% w/w) LAS 12.00 11.60 (linear alkylbenzenesulfonates) AEOS 17.63 4.90 (alkyl ethoxy sulfate), SLES (sodium laurylether sulfate) Soy fatty acid 2.75 2.48 Coco fatty acid 2.75 2.80 AEO(alkyl ethoxylate) 11.00 11.00 Sodium hydroxide 1.75 1.80Ethanol/Propan-2-ol 3.00 2.70/0.30 MPG 6.00 6.00 monopropylene glycolGlycerol 1.71 1.70 TEA (triethanolamine) 3.33 3.30 Sodium formate 1.001.00 Sodium citrate 2.00 2.00 DTMPA 0.48 0.20 (diethylenetriaminepenta-acetic acid) PCA 0.46 0.18 polycarboxylic acid type polymer Phenoxyethanol 0.50 0.50 H₂O, ion exchanged 33.64 33.64Water hardness was adjusted to 15° dH by addition of CaCl₂), MgCl₂, andNaHCO₃ (Ca²⁺:Mg²⁺:HCO₃=4:1:7.5) to the test system. After washing thetextiles were flushed in tap water and dried.

The wash performance was measured as the brightness expressed as theintensity of the light reflected from the sample when illuminated withwhite light. When the sample was stained the intensity of the reflectedlight was lower, than that of a clean sample. Therefore the intensity ofthe reflected light can be used to measure wash performance.

Color measurements were made with a professional flatbed scanner (EPSONExpression 10000XL, EPSON) used to capture an image of the washedtextile.

To extract a value for the light intensity from the scanned images,48→24 Bit Color pixel values from the image were converted into valuesfor red, green and blue (RGB). The intensity value (Int) is calculatedby adding the RGB values together as vectors and then taking the lengthof the resulting vector:

${Int} = \sqrt{r^{2} + g^{2} + b^{2}}$

The term “improved wash performance” of the present experiment isdefined as displaying an alteration of the wash performance of a variantof the present invention relative to the wash performance of thepolypeptide having an amino acid sequence as set forth in SEQ ID NO: 15,The alteration may e.g. be seen as increased stain removal. Improvedwash performance was determined as described above. The wash performancewas considered to be improved if the Improvement Factor (IF) is at least1.0, preferably at least 1.05 in one or more of the conditions listedabove; i.e. either in Model detergent A at 15° C. or 40° C., where thevariant concentration was 0.05 or 0.2 mg/L or in Model detergent J at15° C. or 30° C., where the variant concentration was 0.05 or 0.2 mg/L.The wash conditions were as described above in Tables A and C.

The terms “Delta intensity” or “Delta intensity value” as used hereinrefers to the result of an intensity measurement of a test material,e.g. a swatch CS-28 (Center For Testmaterials BY, P.O. Box 120, 3133 KTVlaardingen, the Netherlands)—. The swatch was measured with a portionof the swatch, washed under identical conditions, as background. Thedelta intensity is the intensity value of the test material washed withamylase subtracting the intensity value of the test material washedwithout amylase.

The wash performance of the variants according to the invention obtainedby AMSA are the following;

A-15- A-15- A-40- A-40- J-15- J-15- J-30- J-30- 0.05 0.2 0.05 0.2 0.050.2 0.05 0.2 Modifications in SEQ ID NO: 13 mg/L mg/L mg/L mg/L mg/Lmg/L mg/L mg/L Reference 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 G182* + D183* +N195F 1.0 1.3 1.1 1.0 1.5 1.3 1.0 1.0 H1* + N54S + V56T + G109A +A174S + G182* + D183* + 2.1 1.9 1.2 1.2 2.6 2.0 1.5 1.3 N195F + V206L +K391A + G476K H1* + N54S + V56T + R87S + G109A + A174S + G182* + 2.8 2.21.3 1.1 2.6 2.4 1.9 1.5 D183* + N195F + V206L + K391A + G476K H1* +T40G + N54S + V56T + G109A + A174S + G182* + 2.2 1.7 1.3 1.1 2.5 2.2 1.91.6 D183* + N195F + V206L + K391A + G476K H1* + T51K + N54S + V56T +G109A + A174S + G182* + 2.7 2.1 1.3 1.1 3.2 2.3 2.0 1.5 D183* + N195F +V206L + K391A + G476K H1* + N54S + V56T + K72R + G109A + A174S + G182* +2.6 2.2 1.2 1.0 2.6 2.5 1.7 1.5 D183* + N195F + V206L + K391A + G476KH1* + N54S + V56T + K72H + G109A + A174S + G182* + 2.5 2.4 1.4 1.1 2.62.3 1.7 1.6 D183* + N195F + V206L + K391A + G476K H1* + A37H + N54S +V56T + G109A + A174S + G182* + 2.8 2.7 1.4 1.2 2.8 2.8 1.9 1.6 D183* +N195F + V206L + K391A + G476K H1* + A37M + N54S + V56T + G109A + A174S +G182* + 2.0 2.3 1.4 1.2 2.7 2.5 2.1 1.6 D183* + N195F + V206L + K391A +G476K H1* + A37V + N54S + V56T + G109A + A174S + G182* + 3.0 2.6 1.4 1.23.1 2.5 2.2 1.7 D183* + N195F + V206L + K391A + G476K H1* + A37S +N54S + V56T + G109A + A174S + G182* + 2.9 2.5 1.2 1.2 2.9 2.3 1.5 1.3D183* + N195F + V206L + K391A + G476K H1* + A37Y + N54S + V56T + G109A +A174S + G182* + 2.6 2.0 1.3 1.2 2.5 2.1 1.5 1.3 D183* + N195F + V206L +K391A + G476K H1* + A37R + N54S + V56T + G109A + A174S + G182* + 2.2 1.91.3 1.2 2.5 2.1 1.4 1.3 D183* + N195F + V206L + K391A + G476K H1* +N54S + V56T + G109A + F113W + A174S + G182* + 2.8 2.2 1.3 1.2 2.7 2.11.5 1.2 D183* + N195F + V206L + K391A + G476K H1* + N54S + V56T +G109A + F113S + A174S + G182* + 2.3 1.9 1.3 1.1 2.4 1.7 1.3 1.2 D183* +N195F + V206L + K391A + G476K H1* + N54S + V56T + G109A + F113N +A174S + G182* + 2.0 1.9 1.2 1.2 2.3 2.1 1.4 1.2 D183* + N195F + V206L +K391A + G476K H1* + N54S + V56T + G109A + F113Y + A174S + G182* + 1.92.1 1.2 1.2 3.1 2.3 1.5 1.3 D183* + N195F + V206L + K391A + G476K H1* +N54S + V56T + G109A + F113R + A174S + G182* + 1.0 1.4 1.2 1.2 2.0 1.81.4 1.3 D183* + N195F + V206L + K391A + G476K H1* + N54S + V56T +G109A + Q118N + A174S + G182* + 1.9 1.8 1.3 1.2 2.9 2.3 1.5 1.3 D183* +N195F + V206L + K391A + G476K H1* + N54S + V56T + G109A + R116Q +A174S + G182* + 2.6 2.0 1.2 1.2 3.5 2.6 1.7 1.4 D183* + N195F + V206L +K391A + G476K H1* + N54S + V56T + G109A + R116V + A174S + G182* + 2.12.0 1.1 1.1 2.7 2.3 1.6 1.3 D183* + N195F + V206L + K391A + G476K H1* +N54S + V56T + G109A + R116K + A174S + G182* + 2.2 2.1 1.2 1.1 2.4 2.21.4 1.3 D183* + N195F + V206L + K391A + G476K H1* + N54S + V56T +G109A + R116W + A174S + G182* + 1.8 2.0 0.7 0.9 1.1 1.9 1.0 1.2 D183* +N195F + V206L + K391A + G476K H1* + N54S + V56T + G109A + R116L +A174S + G182* + 1.8 1.8 1.2 1.1 1.9 2.0 1.3 1.2 D183* + N195F + V206L +K391A + G476K H1* + N54S + V56T + G109A + G142T + A174S + G182* + 1.61.7 1.2 1.1 1.9 2.0 1.3 1.1 D183* + N195F + V206L + K391A + G476K H1* +N54S + V56T + G109A + Q125P + A174S + G182* + 2.1 2.1 1.2 1.1 2.4 2.01.4 1.3 D183* + N195F + V206L + K391A + G476K H1* + N54S + V56T +G109A + Q125K + A174S + G182* + 1.9 1.8 1.3 1.1 2.6 1.9 1.5 1.2 D183* +N195F + V206L + K391A + G476K H1* + N54S + V56T + G109A + A174S +G182* + D183* + 2.3 2.1 1.0 1.0 2.5 2.2 1.4 1.2 N195F + V206L + S381G +K391A + G476K H1* + N54S + V56T + G109A + A174S + G182* + D183* + 2.01.9 1.1 1.0 2.6 1.8 1.5 1.2 N195F + V206L + M246T + K391A + G476K H1* +N54S + V56T + G109A + A174S + G182* + D183* + 1.9 1.9 1.1 1.1 2.8 2.11.5 1.3 N195F + V206L + V213T + K391A + G476K H1* + A37L + N54S + V56T +G109A + A174S + G182* + 2.5 2.2 1.2 1.1 2.5 2.2 1.8 1.4 D183* + N195F +V206L + K391A + G476K H1* + N54S + V56T + G109A + Q118K + A174S +G182* + 1.8 2.0 1.2 1.1 1.5 1.6 1.4 1.2 D183* + N195F + V206L + K391A +G476K H1* + N54S + V56T + G109A + R116A + A174S + G182* + 2.7 2.3 1.21.1 2.4 2.1 1.6 1.3 D183* + N195F + V206L + K391A + G476K H1* + N54S +V56T + G109A + R116H + A174S + G182* + 2.9 2.4 1.3 1.2 2.4 2.3 1.9 1.5D183* + N195F + V206L + K391A + G476K H1* + N54S + V56T + G109A +Q125A + A174S + G182* + 2.1 2.0 1.1 1.2 3.1 2.1 1.5 1.2 D183* + N195F +V206L + K391A + G476K H1* + N54S + V56T + G109A + Q172G + A174S +G182* + 2.6 2.1 1.4 1.2 2.7 2.2 2.1 1.5 D183* + N195F + V206L + K391A +G476K H1* + N54S + V56T + G109A + Q172R + A174S + G182* + 2.6 2.2 1.41.2 2.7 2.4 2.0 1.5 D183* + N195F + V206L + K391A + G476K H1* + N54S +V56T + G109A + A174S + G182* + D183* + 2.4 1.7 1.3 1.2 2.8 1.8 1.7 1.3N195F + V206L + D377S + K391A + G476K H1* + N54S + V56T + G109A +A174S + G182* + D183* + 1.7 1.7 1.2 1.1 2.3 1.5 1.7 1.3 N195F + V206L +D377G + K391A + G476K H1* + N54S + V56T + G109A + A174S + G182* +D183* + 1.9 1.5 1.1 1.1 2.6 1.6 1.4 1.2 N195F + V206L + D377R + K391A +G476K H1* + N54S + V56T + G109A + A174S + G182* + D183* + 2.0 1.9 1.21.0 2.8 1.9 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G476K H1* + N54S + V56T + G109A + A174S +G182* + D183* + 1.8 1.6 1.2 1.1 1.9 1.8 1.6 1.2 N195F + V206L + N270G +K391A + G476K Q169E + Q172K + A174* + D183* + G182* + N195F 1.8 1.2 1.21.0 3.3 1.4 1.5 1.3 H1* + N54S + V56T + G109A + A174S + G182* + D183* +1.8 1.0 1.1 0.9 1.8 1.4 1.5 1.1 N195F + V206L + K269Q + K391A + G476KH1* + W48F + N54S + V56T + G109A + A174S + G182* + 1.8 1.4 1.1 1.0 2.21.7 1.5 1.2 D183* + N195F + V206L + K391A + G476K F113Q + R116Q +D183* + G182* + N195F 1.8 1.7 1.1 1.0 2.1 1.7 1.7 1.4 N54S + V56T +D183* + G182* + N195F 1.8 1.2 0.8 0.9 1.3 1.3 1.0 1.0 H1* + N54S +V56T + G109A + A174T + G182* + D183* + 1.7 1.7 1.2 1.1 2.4 1.9 1.8 1.3N195F + V206L + K391A + G476K H1* + N54S + V56T + G109A + R116W +A174S + G182* + 1.7 1.6 1.2 1.1 1.8 1.8 1.6 1.2 D183* + N195F + V206L +K391A + G476K Q169E + Q172K + G182* + D183* + N195F 1.7 1.4 1.3 1.0 4.91.6 1.8 1.3 G182* + D183* + A186D 1.7 1.6 1.0 1.0 1.6 1.7 1.3 1.1 H1* +N54S + V56T + G109A + A174S + G182* + D183* + 1.7 1.5 1.1 1.0 1.8 1.61.4 1.1 N195F + V206L + V238A + K391A + G476K G182* + D183* + A186N 1.71.8 1.2 1.1 3.8 1.8 1.6 1.5 H1* + N54S + V56T + G109A + A174S + V206L +G182* + 1.7 1.1 1.1 1.0 3.3 1.1 1.3 1.1 D183* + K391A + G476K H1* +N54S + V56T + Q169E + Q172K + A174* + G182* + 1.7 1.4 1.3 1.0 3.6 1.41.8 1.2 D183* + N195F + V206L + K391A + G476K H1* + N54S + V56T +G109A + A174S + G182* + D183* + 1.7 1.7 1.2 1.0 1.7 1.7 1.6 1.3 N195F +V206F + K391A + G476K H1* + N54S + V56T + G109A + G182* + D183* +N195F + 1.7 1.4 1.1 1.0 1.9 1.6 1.2 1.0 V206L + K391A + G476K H1* +N54S + V56T + G109A + Q172K + A174S + G182* + 1.7 1.5 1.1 1.1 3.6 1.61.5 1.3 D183* + N195F + V206L + K391A + G476K H1* + N54S + V56T +G109A + Q172K + A174* + G182* + 1.6 1.4 1.1 1.1 1.6 1.4 1.3 1.1 D183* +N195F + V206L + K391A + G476K H1* + N54S + V56T + G109A + A174N +G182* + D183* + 1.6 1.8 1.2 1.2 4.6 2.0 2.0 1.7 N195F + V206L + K391A +G476K H1* + N54S + V56T + G109A + A174S + A186N + G182* + 1.6 1.8 1.11.0 1.5 1.9 1.7 1.3 D183* + N195F + V206L + K391A + G476K H1* + N54S +V56T + G109A + A174S + G182* + D183* + 1.6 1.5 1.0 1.0 1.7 1.7 1.4 1.2N195F + V206L + F289L + K391A + G476K H1* + N54S + V56T + G109A +A174S + G182* + D183* + 1.6 1.2 1.0 0.8 1.2 1.2 1.3 1.1 N195F + V206L +Y295F + K391A + G476K H1* + N54S + V56T + G109A + A174S + G182* +D183* + 1.6 1.2 1.1 1.0 1.2 1.0 1.2 1.0 N195F + V206L + V291A + K391A +G476K H1* + N54S + V56T + G109A + A174S + G182* + D183* + 1.5 1.4 1.11.0 2.1 1.5 1.3 1.1 N195F + V206L + S244Q + K391A + G476K G182* +D183* + F328L 1.5 1.5 1.1 1.1 1.8 1.8 1.6 1.3 G182* + D183* + N195F +A288V 1.5 1.3 1.2 1.0 1.8 1.6 1.5 1.1 G182* + D183* + A186N + N195F 1.51.6 0.9 0.9 2.4 1.7 1.5 1.2 G182* + D183* + E190P + N195F 1.5 1.4 0.91.0 2.1 1.7 1.1 1.1 W140Y + G182* + D183* + N195F 1.5 1.4 1.1 1.1 1.41.7 1.5 1.3 H1* + N54S + V56T + G109A + A174S + G182* + D183* + 1.5 1.01.1 0.9 1.5 1.0 1.5 1.0 N195F + V206L + A225V + K391A + G476K G182* +D183* + A186D + N195F 1.5 1.7 1.4 1.1 3.3 2.0 1.8 1.6 H1* + N54S +V56T + G109A + A174S + G182* + D183* + 1.5 1.2 1.1 1.0 1.5 1.2 1.3 1.2N195F + V206L + K391A + P473R + G476K H1* + W48Y + N54S + V56T + G109A +A174S + G182* + 1.5 1.3 1.0 1.1 1.2 1.4 1.3 1.2 D183* + N195F + V206L +K391A + G476K H1* + N54S + V56T + G109A + Q169E + Q172K + A174* + 1.51.3 1.4 1.1 3.8 1.4 1.5 1.3 G182* + D183* + N195F + V206L + K391A +G476K G182* + D183* + N195F + V238A 1.5 1.5 1.0 1.1 1.9 1.4 1.1 1.0G182* + D183* + Y295N 1.4 1.1 1.3 1.0 2.5 1.2 1.6 1.2 Q172G + G182* +D183* 1.4 1.4 1.1 1.0 1.4 1.3 1.5 1.3 F113Q + G182* + D183* + N195F 1.40.8 1.0 0.8 1.0 1.0 1.3 1.0 H1* + N54S + V56T + Q98A + G109A + A174S +G182* + 1.4 1.3 1.2 1.0 2.7 1.1 1.5 1.2 D183* + N195F + V206L + K391A +G476K G182* + D183* + N195F + Y295F 1.3 1.3 1.2 1.1 1.3 1.2 1.4 1.1G182* + D183* + A186E 1.3 1.2 1.2 1.0 2.0 1.4 1.4 1.2 H1* + N54S +V56T + G109A + A174S + G182* + D183* + 1.3 1.1 1.2 1.1 2.8 1.2 1.3 1.2N195F + V206Y + K391A + G476K G182* + D183* + N195F + W284H 1.3 1.6 1.11.2 3.3 1.8 1.6 1.6 G182* + D183* + A186Q + N195F 1.3 1.2 1.1 1.0 2.01.7 1.5 1.1 K72R + G182* + D183* 1.3 1.3 1.0 1.0 1.4 1.5 1.3 1.1 D183* +G182* + N195F + V326L 1.3 1.6 1.2 1.2 3.5 1.8 1.5 1.6 D183* + G182* +A186E + N195F 1.3 1.3 1.1 1.0 1.7 1.4 1.5 1.2 Q169E + G182* + D183* +N195F 1.2 1.0 1.1 1.0 1.7 0.8 1.4 1.2 D183* + G182* + N195F + K242Q 1.20.8 0.9 0.9 2.0 1.2 0.9 1.0 G7A + G182* + D183* + N195F 1.2 1.2 1.1 1.01.5 1.6 1.4 1.1 D183* + G182* + N195F + N260G 1.2 1.4 1.0 0.9 1.6 1.21.3 1.1 D183* + G182* + R321A + S323N 1.2 1.3 1.1 1.1 1.2 1.1 1.5 1.2D183* + G182* + W284H 1.2 0.9 1.2 1.0 0.9 1.0 1.1 1.1 H1* + D183* +G182* 1.2 1.5 1.0 1.0 3.6 1.7 1.6 1.3 D183* + G182* + A186H + N195F 1.11.3 1.1 1.0 2.0 1.2 1.4 1.0 D183* + G182* + F289V 1.1 1.3 1.0 1.0 2.21.3 1.7 1.4 D183* + G182* + K391A 1.1 0.7 1.0 0.8 0.7 0.7 1.0 0.8D183* + G182* + S304R 1.1 1.2 0.9 0.9 0.6 0.9 1.0 1.0 W167F + G182* +D183* + N195F 1.1 1.0 1.0 0.9 3.3 1.1 1.3 1.1 F113Q + R116H + D183* +G182* 1.1 0.7 1.0 0.8 1.2 0.8 1.3 0.9 D183* + G182* + N270G 1.1 1.0 0.90.9 1.0 1.3 1.0 1.0 D183* + G182* + S244Q 1.0 1.1 1.1 0.9 1.8 1.6 1.51.0 H1* + N54S + V56T + G109A + A174S + G182* + D183* + 1.0 1.0 1.1 1.00.6 0.6 0.9 0.9 G184T + N195F + V206L + K391A + G476K D183* + G182* +N195F + Y295N 1.0 1.1 1.0 1.0 1.6 0.9 1.2 1.3 W48F + D183* + G182* 1.00.9 1.0 0.9 1.8 1.0 1.3 1.0 H1* + N54S + V56T + G109A + A174S + G182* +D183* + 1.0 1.2 1.0 1.0 1.8 1.1 1.2 1.1 N195F + V206L + G255A + K391A +G476K D183* + G182* + A186Q 1.0 0.7 1.1 0.9 0.4 0.5 1.0 0.9 W140Y +D183* + G182* 0.9 0.6 0.9 0.9 0.5 0.9 1.1 1.0 D183* + G182* + K242Q 0.90.8 1.0 0.9 0.8 0.9 1.0 1.1 D183* + G182* + V206L 0.9 0.8 0.9 0.9 1.10.9 0.9 0.9 D183* + G182* + N195F + V206F 0.9 0.9 0.9 1.1 0.5 0.8 1.11.0 Q169E + D183* + G182* 0.9 0.8 1.0 0.9 1.1 0.8 0.9 0.9 D183* +G182* + N195F + R320A 0.8 0.9 1.1 1.0 0.8 0.9 1.0 1.0 G182* + D183* +G184T + N195F 0.8 1.1 0.9 1.0 0.9 1.0 1.2 1.0 D183* + G182* + G184T 0.80.9 1.0 0.9 0.7 0.8 1.0 1.1 N54S + V56T + D183* + G182* 0.8 0.8 1.1 1.00.9 0.7 1.1 0.9 D183* + G182* + P473R 0.8 0.9 1.0 1.0 1.1 0.8 1.0 1.0W48Y + D183* + G182* 0.8 0.9 1.1 1.1 1.0 0.6 1.0 0.9 D183* + G182* +R323A 0.8 0.8 0.9 1.0 1.1 0.8 1.1 0.8 G7A + D183* + G182* 0.8 0.8 1.10.9 1.3 1.1 1.2 1.0 G109A + D183* + G182* 0.8 0.8 0.8 0.8 0.0 0.6 1.01.1 W167F + D183* + G182* 0.7 0.7 1.0 0.9 1.4 0.9 1.1 1.0 H1* + N54S +V56T + G109A + Q169E + Q172K + A174S + 0.7 0.7 0.8 0.9 1.1 0.5 0.8 0.8G182* + D183* + N195F + V206L + K391A + G476K A174S + D183* + G182* 0.71.2 0.8 0.9 2.2 0.9 1.1 1.3 R116Q + D183* + G182* 0.7 0.7 0.9 0.9 0.70.6 1.1 0.9 D183* + G182* + N195F + V291A 0.7 0.9 1.0 1.1 0.6 0.9 0.91.0 Q172K + D183* + G182* 0.7 0.9 0.9 1.0 0.4 0.5 1.1 0.9 N54S + D183* +G182* 0.7 1.2 1.0 1.1 1.7 1.1 1.0 1.3 D183* + G182* + N195F + S323N 0.70.9 0.8 0.9 1.8 1.0 1.0 1.0 D183* + G182* + N195F + M246V 0.7 0.8 1.11.0 0.6 0.5 0.9 0.9 W48Y + D183* + G182* + N195F 0.6 1.2 1.1 1.1 2.0 1.51.2 1.4 D183* + G182* + N195F + S304R 0.6 1.1 0.7 1.0 1.6 0.7 1.0 1.2V56T + D183* + G182* 0.3 0.8 0.2 0.6 1.9 0.6 0.3 0.7 A-15- A-15- A-40-A-40- J-15- J-15- J-30- J-30- 0.05 0.2 0.05 0.2 0.05 0.2 0.05 0.2Modifications in SEQ ID NO: 14 mg/L mg/L mg/L mg/L mg/L mg/L mg/L mg/LReference 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 G182* + D183* + N195F 1.4 1.21.0 1.0 1.2 1.3 1.1 1.1 H1* + G182* + D183* + N195F 1.1 1.0 1.0 1.1 1.11.0 1.1 1.1 N54S + G182* + D183* + N195F 1.2 1.1 0.9 1.1 1.3 1.1 1.1 1.1V56T + G182* + D183* + N195F 1.4 1.1 1.0 1.0 1.5 1.2 1.1 1.1 G182* +D183* + N195F + I405L 1.1 1.1 1.0 1.0 1.1 1.1 1.0 1.0 H1* + N54S +V56T + G109A + A174S + G182* + D183* + 1.0 1.1 0.9 0.9 1.4 1.0 1.1 0.9N195F + V206L + I405L + A421H + A422P + A428T + D476K A174S + G182* +D183* + N195F 1.2 1.0 1.0 0.9 0.9 0.9 1.0 1.0 H1* + N54S + V56T +G109A + A174S + G182* + D183* + 1.4 1.3 1.1 1.0 1.6 1.3 1.3 1.1 N195F +V206L + I405L + A421H + A422P + A428T H1* + N54S + V56T + G109A +A174S + D183* + N195F + 1.2 1.3 1.0 1.0 1.6 1.3 1.2 1.1 V206L + K391A +I405L + A421H + A422P + A428T H1* + N54S + V56T + G109A + A174S +G182* + D183* + 1.3 1.3 1.1 1.0 1.4 1.3 1.1 1.0 N195F + V206L + K391A +I405L + A421H + A422P + A428T + D476K H1* + N54S + V56T + G109A +A174S + G182* + D183* + 1.2 1.1 1.1 1.0 1.4 1.2 1.2 1.1 N195F + V206L +K391A + I405L + A421H + A422P + A428T + D476G H1* + N54S + V56T +G109A + A174S + G182* + D183* + 1.3 1.3 1.0 1.0 1.5 1.2 1.1 1.0 N195F +V206L + K391A + I405L + A421H + A422P + A428T + D476K + G477S H1* +N54S + V56T + G109A + A174S + G182* + D183* + 1.3 1.2 1.0 1.0 1.5 1.21.2 1.0 N195F + V206L + K391A + I405L + A421H + A422P + A428T + D476KH1* + N54S + V56T + K72R + G109A + W167F + A174S + 1.1 1.2 1.0 1.1 1.41.4 1.3 1.1 G182* + D183* + N195F + V206L + I405L + A421H + A422P +A428T H1* + N54S + V56T + G109A + A174S + G182* + D183* + 0.9 1.2 1.10.9 1.3 1.2 1.3 1.0 N195F + V206L + S280Q + H321Y + I405L + A421H +A422P + A428T H1* + N54S + V56T + G109A + A174S + G182* + D183* + 1.11.2 1.0 1.0 1.2 1.1 1.1 1.0 N195F + V206L + S304N + I405L + A421H +A422P + A428T + D476K H1* + N54S + V56T + G109A + A174S + G182* +D183* + 1.2 1.2 1.0 1.0 1.2 1.0 1.0 0.9 N195F + V206L + K391A + I405L +A421H + A422P + A428T + D476K + G477A H1* + N54S + V56T + G109A +A174S + G182* + D183* + 1.6 1.4 1.1 1.1 1.9 1.4 1.3 1.2 N195F + V206L +K391A + I405L + A421H + A422P + A428T + D476G + G477T H1* + N54S +V56T + G109A + F113Q + R116Q + Q172N + 0.9 1.2 0.8 1.1 0.8 1.7 0.9 1.1A174S + G182* + D183* + N195F + V206L + I405L + A421H + A422P + A428TH1* + N54S + V56T + G109A + A174S + G182* + D183* + 1.7 1.3 1.1 1.0 1.91.4 1.3 1.1 N195F + V206L + K391A + I405L + A421H + A422P + A428T +G477Q H1* + N54S + V56T + G109A + A174S + G182* + D183* + 1.5 1.4 1.11.0 1.9 1.4 1.3 1.1 N195F + V206L + K391A + I405L + A421H + A422P +A428T + G477A H1* + N54S + V56T + G109A + A174S + G182* + D183* + 1.31.3 1.0 1.0 1.7 1.2 1.1 1.0 N195F + V206L + K391A + I405L + A421H +A422P + A428T + D476K + G477Q H1* + N54S + V56T + G109A + A174S +G182* + D183* + 1.5 1.3 1.1 1.1 1.7 1.4 1.3 1.2 N195F + V206L + K391A +I405L + A421H + A422P + A428T + D476N H1* + N54S + V56T + G109A +A174S + G182* + D183* + 1.5 1.3 1.1 1.0 1.7 1.3 1.3 1.2 N195F + V206L +K391A + I405L + A421H + A422P + A428T + D476Y H1* + N54S + V56T +G109A + A174S + G182* + D183* + 1.5 1.2 1.1 1.1 2.2 1.4 1.4 1.1 N195F +V206I + I405L + A421H + A422P + A428T H1* + N54S + V56T + G109A +Q172D + A174S + G182* + 1.4 1.3 1.1 1.0 2.8 2.0 1.4 1.2 D183* + N195F +A204G + V206L + I405L + A421H + A422P + A428T H1* + N54S + V56T + K72R +G109A + T134E + A174S + 1.3 1.1 1.0 1.0 2.1 2.1 1.3 1.0 G182* + D183* +N195F + A204G + V206L + G255A + I405L + A421H + A422P + A428T H1* +N54S + V56T + G109A + F113Q + R116H + T165G + 1.3 1.3 1.0 1.0 2.9 1.91.3 1.1 Q172G + A174S + G182* + D183* + N195F + V206L + I405L + A421H +A422P + A428T H1* + N54S + V56T + G109A + F113Q + Q172N + A174S + 1.31.3 1.1 1.1 1.9 2.2 1.5 1.3 G182* + D183* + N195F + V206L + I405L +A421H + A422P + A428T H1* + N54S + V56T + K72R + G109A + T134E + A174S +1.4 1.3 1.1 1.1 2.5 2.3 1.5 1.3 G182* + D183* + N195F + G196R + V206L +G255A + I405L + A421H + A422P + A428T + N475S H1* + N54S + V56T +G109A + T134E + A174S + G182* + 1.8 1.5 1.2 1.0 2.3 1.8 1.5 1.2 D183* +N195F + V206L + I405L + A421H + A422P + A428T H1* + T40D + N54S + V56T +G109A + A174S + G182* + 2.0 1.5 1.2 1.1 1.8 1.6 1.5 1.3 D183* + N195F +V206L + I405L + A421H + A422P + A428T H1* + N54S + V56T + G109A +F113Q + N125D + A174S + 2.1 1.6 1.3 1.0 2.2 1.7 1.5 1.2 G182* + D183* +N195F + V206L + I405L + A421H + A422P + A428T H1* + N54S + V56T + A60V +G109A + R116Q + A174S + 1.6 1.6 1.1 1.0 1.9 1.6 1.4 1.2 G182* + D183* +N195F + V206L + I405L + A421H + A422P + A428T H1* + N54S + V56T +G109A + R116V + A174S + G182* + 1.4 1.4 1.0 1.0 2.1 1.4 1.4 1.2 D183* +N195F + V206L + I405L + A421H + A422P + A428T H1* + N54S + V56T +G109A + R116Q + G133Q + T165G + 1.1 1.4 1.0 1.1 2.0 2.3 1.5 1.3 Q172G +A174S + G182* + D183* + N195F + V206L + I405L + A421H + A422P + A428TH1* + N54S + V56T + G109A + F113Q + R116H + Q172G + 1.7 1.6 1.2 1.1 3.01.9 1.5 1.2 A174S + G182* + D183* + N195F + V206L + I405L + A421H +A422P + A428T H1* + N54S + V56T + G109A + F113Q + R116Q + Q172G + 1.41.5 1.1 1.1 2.1 1.8 1.3 1.2 A174S + G182* + D183* + N195F + V206L +I405L + A421H + A422P + A428T + G448D H1* + N54S + V56T + G109A +F113Q + R116H + Q172N + 2.2 1.6 1.3 1.2 2.5 1.6 1.6 1.3 A174S + G182* +D183* + N195F + V206L + I405L + A421H + A422P + A428T H1* + N54S +V56T + K72R + G109A + T134E + W167F + 2.2 1.6 1.3 1.2 2.4 1.6 1.7 1.2Q172N + A174S + G182* + D183* + N195F + V206L + G255A + A265G + I405L +A421H + A422P + A428T H1* + N54S + V56T + K72R + G109A + R116Q + W167F +2.0 1.6 1.2 1.2 2.3 1.6 1.7 1.2 Q172R + L173V + A174S + G182* + D183* +N195F + V206L + A265G + I405L + A421H + A422P + A428T H1* + N54S +V56T + K72R + G109A + R116Q + W167F + 2.1 1.4 1.3 1.2 2.3 1.6 1.7 1.2Q172R + A174S + G182* + D183* + N195F + V206L + I405L + A421H + A422P +A428T H1* + N54S + V56T + K72R + G109A + F113Q + T134E + 2.0 1.5 1.1 1.12.6 1.9 1.4 1.2 W167F + Q172G + A174S + G182* + D183* + N195F + V206L +G255A + I405L + A421H + A422P + A428T H1* + N54S + V56T + K72R + G109A +F113Q + R116H + 1.7 1.6 1.0 0.9 1.8 1.5 1.1 1.1 W167F + Q172G + L173V +A174S + G182* + D183* + G184T + N195F + V206L + I405L + A421H + A422P +A428T H1* + N54S + V56T + G109A + F113Q + W167F + Q172G + 1.2 1.2 1.00.9 2.2 1.3 1.2 1.1 A174S + G182* + D183* + N195F + V206L + I405L +A421H + A422P + A428T H1* + N54S + V56T + K72R + G109A + A174S + G182* +1.5 1.2 1.2 1.0 2.2 1.1 1.5 1.1 D183* + N195F + V206L + G255A + I405L +A421H + A422P + A428T H1* + N54S + V56T + G109A + F113Q + R116Q +A174S + 1.6 1.3 1.1 1.0 1.4 1.2 1.3 1.1 G182* + D183* + N195F + V206L +I405L + A421H + A422P + A428T H1* + N54S + V56T + K72R + G109A + F113Q +F116H + 1.8 1.6 1.0 1.0 0.9 1.4 0.9 1.1 W167F + Q172G + L173V + A174S +G182* + D183* + N195F + V206L + I405L + A421H + A422P + A428T H1* +N54S + V56T + K72R + G109A + F113Q + R116Q + 1.8 1.5 1.1 1.0 1.9 1.5 1.31.1 W167F + Q172G + A174S + G182* + D183* + G184T + N195F + V206L +I405L + A421H + A422P + A428T H1* + N54S + V56T + G109A + F113Q +R116Q + W167F + 2.0 1.5 1.0 1.0 1.8 1.5 1.2 1.0 Q172G + A174S + G182* +D183* + N195F + A204G + V206L + I405L + A421H + A422P + A428T H1* +N54S + V56T + G109A + F113Q + R116H + W167F + 1.5 1.3 0.9 0.9 1.4 1.31.2 1.1 Q172G + A174S + G182* + D183* + N195F + V206L + A265G + I405L +A421H + A422P + A428T H1* + N54S + V56T + G109A + R116Q + A174S +G182* + 1.8 1.6 1.0 0.9 1.6 1.3 1.4 1.1 D183* + N195F + V206L + I405L +A421H + A422P + A428T H1* + N54S + V56T + A60V + G109A + R116Q + W167F +1.4 1.4 0.7 0.9 1.1 1.3 0.8 1.0 Q172N + L173V + A174S + G182* + D183* +N195F + V206L + I405L + A421H + A422P + A428T H1* + A37H + N54S + V56T +A60V + G109A + R116Q + 1.9 1.6 1.1 1.1 1.7 1.6 1.4 1.2 T165G + A174S +G182* + D183* + N195F + V206L + I405L + A421H + A422P + A428T H1* +N54S + V56T + G109A + A174S + M105F + G182* + 1.4 1.2 1.0 1.0 1.5 1.21.2 1.0 D183* + N195F + V206L + L228I + R320A + S323N + I405L + A421H +A422P + A428T H1* + N54S + V56T + K72R + G109A + F113Q + T134E + 1.8 1.51.1 1.0 1.7 2.1 1.4 1.2 A174S + G182* + D183* + N195F + V206L + G255A +I405L + A421H + A422P + A428T H1* + N54S + V56T + K72R + G109A + R116Q +V120L + 2.1 1.8 1.2 1.1 2.8 2.5 1.6 1.3 A174S + G182* + D183* + G184T +N195F + V206L + I405L + A421H + A422P + A428T H1* + N54S + V56T +G109A + F113Q + R116H + W167F + 2.6 1.9 1.2 1.1 2.8 2.6 1.6 1.3 Q172G +L173V + A174S + G182* + D183* + N195F + V206L + I405L + A421H + A422P +A428T H1* + N54S + V56T + G109A + F113Q + R116Q + Q172N + 2.3 1.6 1.11.1 3.0 2.1 1.5 1.3 A174S + G182* + D183* + N195F + V206L + A265G +I405L + A421H + A422P + A428T H1* + A37H + N54S + V56T + A60V + G109A +R116Q + 2.1 1.7 1.2 1.1 2.5 2.1 1.5 1.2 W167F + Q172R + A174S + G182* +D183* + N195F + V206L + I405L + A421H + A422P + A428T

Example 4: Wash Performance of a Subset of Variants According to theInvention (AMSA)

The following variants have been tested as described above. The colormeasurements were done by use of a professional flatbed scanner (KodakiQsmart, Kodak) used to capture an image of the washed textile and witha controlled digital imaging system (DigiEye) for capture an image ofthe washed melamine plates.

To extract a value for the light intensity from the scanned images,24-bit pixel values from the image are converted into values for red,green and blue (RGB). The intensity value (Int) is calculated by addingthe RGB values together as vectors and then taking the length of theresulting vector:

${Int} = \sqrt{r^{2} + g^{2} + b^{2}}$

The results obtained were the following;

A-15- A-15- A-40- A-40- J-15- J-15- J-30- J-30- 0.05 0.2 0.05 0.02 0.050.2 0.05 0.2 Modifications in SEQ ID NO: 13 mg/L mg/L mg/L mg/L mg/Lmg/L mg/L mg/L Reference 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 G182* + D183* +N195F + V206F + N260P + L312I + L313I + R320A + T355L + 0.7 1.0 0.6 0.71.3 0.9 0.8 1.0 L389I + T400P G132* + D183* + N195F 0.1 0.7 1.0 1.0 1.00.8 1.0 1.0 H1* + N54S + V56T + G109A + A174S + G182* + D183* + N195F +V206L + K391A + 1.7 1.9 1.7 1.3 2.5 1.9 1.2 1.2 G476K H1* + G50A +T51A + V56T + G109A + A174S + G182* + D183* + N195F + V206L + 1.5 1.61.5 1.4 2.5 1.6 1.3 1.2 G476K H1* + N54S + V56T + M105F + G109A +A174S + G182* + D183* + N195F + V206L + 2.5 2.2 1.6 1.4 3.8 1.9 1.2 1.1R320A + S323N + K391A + G476K H1* + T40K + N54S + V56T + G109A + G149H +A174S + G182* + D183* + N195F + 0.9 1.2 1.0 1.0 0.8 1.2 0.9 1.1 V206L +K391A + G476K H1* + N54S + V56T + K72R + G109A + A174S + G182* + D183* +N195F + V206L + 1.9 1.7 1.4 1.4 2.8 1.5 1.2 1.1 G255A + K391A + G476KH1* + N16H + V17L + N54S + V56T + G109A + A174S + G182* + D183* +N195F + 2.6 1.8 1.7 1.4 3.6 1.8 1.3 1.1 V206L + K391A + G476K H1* +Q22N + N54S + V56T + G109A + A174S + G182* + D183* + N195F + V206L + 2.51.9 1.8 1.4 3.8 2.1 1.3 1.1 K391A + G476K H1* + Q32S + N54S + V56T +G109A + A174S + G182* + D183* + N195F + V206L + 2.3 1.9 1.9 1.5 3.3 2.01.2 1.2 K391A + G476K H1* + H28N + N54S + V56T + G109A + A174S + G182* +D183* + N195F + V206L + 2.7 1.7 1.6 1.5 4.2 2.0 1.3 1.1 K391A + G476KH1* + N29S + N54S + V56T + G109A + A174S + G182* + D183* + N195F +V206L + 1.6 1.3 1.3 1.4 2.6 1.6 1.2 1.0 K391A + G476K H1* + H28N +N29S + N54S + V56T + G109A + A174S + G182* + D183* + N195F + 1.8 1.9 1.81.4 3.1 1.8 1.2 1.1 V206L + K391A + G476K H1* + N54S + V56T + G109A +A174S + R176K + N195F + V206L + K391A + G476K 2.3 2.0 1.7 1.5 5.1 1.91.3 1.2 H1* + N54S + V56T + G109A + Q169E + Q172K + A174* + R176K +N195F + V206L + 3.8 2.4 2.1 1.7 5.6 2.8 1.4 1.2 K391A + G476K H1* +N54S + V56T + G109A + A174S + N175G + N195F + V206L + K391A + G476K 2.61.8 1.8 1.4 4.9 2.0 1.3 1.2 H1* + N54S + V56T + G109A + A174S + N195F +V206L + V291A + Y295N + Q299T + 1.7 1.4 1.4 1.3 2.7 1.6 1.0 1.1 K391A +G476K H1* + N54S + V56T + G109A + A174S + N195F + V206L + K269S +A274K + K391A + 1.7 1.4 1.6 1.2 1.4 1.8 1.0 1.0 G476K H1* + N54S +V56T + G109A + A174S + N195F + V206L + L235I + K391A + G476K 2.6 1.5 2.01.3 1.3 2.1 1.0 1.1 H1* + N54S + V56T + G109A + A174S + N195F + V206L +L235V + V238A + K391A + 2.8 1.4 1.7 1.2 0.6 2.2 1.1 1.0 G476K H1* +N54S + V56T + G109A + A174S + N195F + V206L + Q365S + K391A + G476K 1.91.5 1.9 1.3 2.0 1.7 1.2 1.0 H1* + N54S + V56T + G109A + A174S + N195F +V206L + K391A + H402R + G476K 2.2 1.4 2.0 1.2 0.6 1.2 1.1 1.1 H1* +N54S + V56T + G109A + A174S + N19SF + V206L + R320S + H321N + K391A +5.6 2.7 2.5 1.6 4.2 2.9 1.2 1.2 G476K H1* + N54S + V56T + G109A +Q169E + Q172K + A174* + N195F + V206L + K391A + 3.8 2.6 3.0 1.7 3.6 2.81.3 1.2 G476K H1* + N54S + V56T + G109A + Q125S + A174S + N195F +V206L + K391A + G476K 3.1 2.2 2.4 1.4 2.0 2.3 1.3 1.1 H1* + N54S +V56T + G109A + A174S + N19SF + V206L + L235V + K391A + G476K 4.2 1.9 1.91.5 1.8 2.4 1.0 1.0 H1* + N54S + V56T + G109A + A174S + N195F + V206L +A265G + K391A + G476K 4.2 1.5 2.2 1.4 1.2 2.6 1.1 1.1 H1* + T51Q +N54S + V56T + G109A + A174S + N195F + Y203F + V206L + K391A + 3.7 2.12.6 1.6 3.6 2.7 1.3 1.1 G476K H1* + N54S + V56T + G109A + Q169E +Q172K + A174* + N175Q + N195F + V206L + 4.0 2.0 2.7 1.5 3.3 2.8 1.2 1.2K391A + G476K H1* + H28N + N54S + V56T + G109A + A174S + G182* + D183* +N195F + V206L + 4.5 2.3 2.5 1.6 3.1 2.7 1.2 1.1 K391A + G476K H1* +N54S + V56T + G109A + T134E + A174S + G182* + D183* + N195F + V206L +3.9 2.1 2.6 1.6 3.3 3.0 1.4 1.1 K391A + G476K H1* + N54S + V56T +G109A + A174S + G182* + D183* + N195F + V206L + D377H + 5.3 2.9 3.0 1.73.8 2.9 1.3 1.2 K391A + G476K H1* + G50A + T51A + N54S + V56T + G109A +A174S + G182* + D183* + N195F + 4.4 2.1 2.3 1.4 2.6 2.3 1.3 1.2 V206L +K391A + G476K H1* + G7K + N54S + V56T + G109A + A174S + G182* + D183* +N195F + V206L + 4.1 2.3 2.7 1.6 2.4 2.5 1.3 1.2 K391A + G476K H1* +N54S + V56T + G109A + A174S + G182* + D183* + N195F + M202V + V206L +2.7 1.9 1.4 1.4 1.9 2.2 0.9 1.0 K391A + G476K H1* + N54S + V56T +M105F + G109A + A174S + N195F + V206L + M246F + K391A + 3.7 2.1 2.4 1.52.7 2.5 1.2 1.1 G476K H1* + N16H + V17L + N54S + V56T + G109A + A174S +G182* + D183* + N195F + 4.5 2.7 1.8 1.4 4.3 2.2 1.5 1.3 V206L + D377H +K391A + G476K H1* + N54S + V56T + G109A + A174S + N195F + V206L 1.1 1.91.3 1.1 3.0 1.9 1.3 1.1 H1* + T51G + N54S + V56T + G109A + A174S +N195F + Y203G + V206L + K391A + 2.2 1.8 1.1 1.0 2.7 2.0 0.9 1.1 G476KH1* + T51G + N54S + V56T + G109A + G110N + A174S + N195F + V206L +K391A + 1.6 2.1 1.0 1.1 1.9 1.9 1.1 1.1 G476K H1* + N54S + V56T +G109A + Q125S + A174S + N175G + N195F + V206L + K391A + 2.0 2.3 1.5 1.22.6 1.8 1.3 1.2 G476K H1* + N54S + V56T + G109A + A174S + N195F +V206L + A265G + V291A + F328L + 0.7 2.1 1.1 1.0 1.8 1.7 1.0 1.1 K391A +G476K H1* + N54S + V56T + G109A + A174S + N195F + V206L + M246F +A265G + V291A + 3.9 2.6 1.9 1.4 4.0 2.1 1.5 1.2 F328L + Q365S + K391A +G476K H1* + N16Y + N54S + V56T + G109A + R116H + A174S + N195F + V206L +G337E + 4.8 3.5 2.0 1.5 4.9 2.7 1.5 1.3 D377H + K391A + G476K H1* +I9L + N54S + V56T + G109A + Q125S + V131T + A174* + V206L + Y267F + 3.12.9 1.4 1.2 2.5 2.0 1.2 1.1 F289H + Q361E + K391A + G476K

The invention described and claimed herein is not to be limited in scopeby the specific aspects herein disclosed, since these aspects areintended as illustrations of several aspects of the invention. Anyequivalent aspects are intended to be within the scope of thisinvention. Indeed, various modifications of the invention in addition tothose shown and described herein will become apparent to those skilledin the art from the foregoing description. Such modifications are alsointended to fall within the scope of the appended claims. In the case ofconflict, the present disclosure including definitions will control.

1. A variant of a parent polypeptide having alpha-amylase activity,wherein said variant is a fusion polypeptide which has an improved washperformance at low temperature, and wherein said variant hasalpha-amylase activity.
 2. The variant according to claim 1, whereinsaid low temperature is 5° C. to 40° C.
 3. The variant according toclaim 1, wherein said improved wash performance has an ImprovementFactor (IF) of ≥1 when compared to said parent polypeptide havingalpha-amylase activity.
 4. The variant according to claim 1, whereinsaid parent polypeptide comprises an A and a B domain comprising theamino acid sequence of SEQ ID NO: 10, or an A and a B domain having atleast 80%, at least 85%, at least 90%, at least 95%, or at least 97%sequence identity to SEQ ID NO: 10, and a C domain of a low temperaturealpha-amylase.
 5. The variant according to claim 1, wherein said parentpolypeptide comprises a C domain comprising the amino acid sequence ofSEQ ID NOs: 11 or 12, or a C domain having at 80%, at least 85%, atleast 90%, at least 95%, at least 97%, sequence identity to SEQ ID NO:11 or
 12. 6. The variant according to claim 1, wherein said parentpolypeptide comprises the amino acid sequence of SEQ ID NOs: 13 or 14,or a sequence having at least 80%, at least 85%, at least 90%, at least95%, or at least 97% sequence identity to SEQ ID NOs: 13 or
 14. 7. Thevariant according to claim 1, wherein said variant comprises an aminoacid sequence having at least 65%, at least 70%, at least 75%, at least80%, at least 85%, at least 90%, at least 95%, at least 97%, or at least99%, but less than 100% sequence identity to any one of the SEQ ID NOs:4, 7, 13, 14, or
 15. 8. The variant according to claim 1, wherein said Aand B domains comprise a modification in one or more of the followingpositions corresponding to positions: H1, T5, G7, Q11, N16, V17, Q32,A37, T40, P45, W48, G50, T51, N54, V56, A60, K72, R87, Q98, M105, G109,F113, R116, Q118, Q125, G133, T134, W140, G142, G149, T165, W167, Q169,R171, Q172, L173, A174, G184, A186, E190, T193, N195, G196, A204, V206,P211, I214, V215, L217, L219, A225, L228, L235, V238, K242, S244, M246,M248, L250, G255, Q256, N260, A263, V264, A265, Y267, K269, N270, G273,S280, W284, T285, M286, F289, V291, Y295, Q299, S304, R320, H321, S323,H324, V326, F328, T334, D337, Q345, G346, G348, T355, S376, D377, D379,Y382, S383, Q385, K391, K393, and Q395 of SEQ ID NOs: 7 or
 10. 9. Thevariant according to claim 7, wherein said modifications in one or morepositions correspond to the following: H1*, T5K, G7K, G7A, Q11H, N16S,N16H, V17L, Q32S, A37H, A37M, A37V, A37S, A37Y, A37R, A37L, T40D, T40G,T40K, P45A, W48G, W48Y, W48F, G50A, T51K, T51E, T51G, T51A, T51S, T51G,T51D, N54S, V56T, A60V, K72R, K72H, K72S, K72Q, K72E, K72N, K72A, K72M,R87S, Q98S, Q98A, M105F, M105I, M105V, M105L, G109A, G109S, F113W,F113S, F113N, F113Y, F113R, F113L, F113Q, R116Q, R116V, R116K, R116W,R116L, R116A, R116H, R116M, R116E, R116S, R116I, R116G, Q118N, Q118K,Q118G, Q118S, Q118F, Q118R, Q125P, Q125K, Q125A, Q125T, N125D, G133S,F133Q, T134E, W140Y, G142T, G149Q, T165S, T165G, T165V, W167I, W167G,W167F, W167R, W167S, W167H, W167L, W167M, W167Y, Q169E, R171H, Q172G,Q172R, Q172N, Q172D, Q172Y, Q172M, Q172S, Q172T, Q172K, Q172H, Q172E,L173V, L173G, L173H, L173A, L173I, L173P, L173T, L173F, L173M, A174S,A174D, A174P, A174M, A174T, A174H, A174K, A174G, A174Q, A174N, A174V,A174L, G184T, A186D, A186N, A186E, A186Q, A186H, E190P, T193K, N195F,G196R, A204T, A204V, A204S, A204G, V206L, V206S, V206Y, P211D, I214G,I214H, I214S, I214T, I214L, I214E, I214W, V215T, L217T, L217Q, L219V,L219H, A225V, L228I, L235V, L235A, V238A, V238T, V238G, K242Q, S244Q,M246L, M246A, M246I, M246F, M246V, M246S, M248T, L250I, L250V, L250T,L250A, L250F, L250M, G255N, G255A, G255S, Q256A, N260G, A263G, V264I,V264T, A265G, Y267I, Y267M, Y267H, Y267L, K269Q, N270G, N270T, G273R,S280W, S280L, S280T, S280A, S280K, S280Q, W284H, T285L, T285Q, M286F,M286L, A288L, A288V, F289I, F289L, V291G, V291A, V291T, Y295N, Y295F,Q299V, S304N, S304R, R320A, R320V, H321Y, S323N, H324L, V326L, F328L,F328M, F328V, F328I, T334S, D337H, Q345D, G346T, G346D, G346P, G348S,G348P, T355L, T355F, S376H, S376T, S376V, D377H, D377S, D377A, D377Q,D379S, D379G, D379R, D379A, Y382M, Y382I, Y382L, Y382F, S383G, S383A,Q385L, K391A, K391Y, K391V, K391M, K391E, K391D, K391R, K391H, K391W,K391I, K391Q, K391L, K393Y, K393R, K393Q, K393S, and Q395P, wherein saidpositions correspond to positions of SEQ ID NOs: 7 or
 10. 10. Thevariant according to claim 1, wherein said C domain comprises analteration in one or more of the following positions corresponding topositions: A420, G423, T444, A445, Q449, T459, P473, C474, G476, G477,and K484 of SEQ ID NO: 13 or I405, A421, A422, A428, R439, G448, W467,D476, and G477 of SEQ ID NO:
 14. 11. The variant according to claim 9,wherein said alteration in one or more positions correspond to thefollowing: T400P, H402R, A420Q, A420S, A420K, A420L, G423H, T444Q,T444S, T444D, T444Y, T444H, T444V, T444R, T444A, A445Q, Q449T, T459N,P473R, P473A, P473G, P473T, P473K, C474V, G476K, G477A, G477Q, K484A,K484G, K484P, K484E, K484Q, and K484S, wherein said positions correspondto positions of SEQ ID NO: 13; or I405L, A421H, A422P, A428T, G448D,D476K, D476G, D476N, D476Y, G477S, G477A, G477T, and G477Q, wherein saidpositions correspond to positions of SEQ ID NO:
 14. 12. The variantaccording to claim 1, wherein said variant comprises: a) a deletionand/or a substitution at two or more positions corresponding topositions R181, G182, D183, and G184 of the amino acid sequence as setforth in SEQ ID NOs: 7 or 10, and b) an alteration at one or morepositions corresponding to positions H1, T5, G7, Q11, N16, V17, Q32,A37, T40, P45, W48, G50, T51, N54, V56, K72, R87, Q98, M105, G109, F113,R116, Q118, Q125, G133, T134, W140, G142, G149, T165, W167, Q169, R171,Q172, L173, A174, G184, A186, E190, T193, N195, A204, V206, P211, I214,V215, L217, L219, A225, L235, V238, K242, S244, M246, M248, L250, G255,Q256, N260, A263, V264, Y267, K269, N270, G273, S280, W284, T285, M286,F289, V291, Y295, Q299, R320, H321, S323, H324, V326, F328, T334, D337,Q345, G346, G348, T355, S376, D377, D379, Y382, S383, Q385, K391, K393,Q395, A420, G423, T444, A445, Q449, T459, P473, C474, G476, G477, andK484 of SEQ ID NO: 13; or H1, A37, T40, N54, V56, A60, K72, G109, F113,R116, N125, F133, T134, T165, Q169, Q172, L173, A174, G184, A186, N195,G196, A204, V206, A225, L228, K242, S244, G255, N260, A265, K269, S280,W284, Y295, S304, R320, H321, S323, V326, K391, I405, A421, A422, A428,R439, G448, W467, D476, and G477 of SEQ ID NO:
 14. 13. The variantaccording to claim 11, wherein the deletion a) is selected from thegroup consisting of R181+G182, R181+D183, R181+G184, G182+D183,G182+G184, or D183+G184.
 14. The variant according to claim 11, whereinsaid variant comprises one or more of the following alterations: H1*,T5K, G7K, G7A, Q11H, N16S, N16H, V17L, Q32S, A37H, A37M, A37V, A37S,A37Y, A37R, A37L, T40G, T40K, P45A, W48G, W48Y, W48F, G50A, T51K, T51E,T51G, T51A, T51S, T51G, T51D, N54S, V56T, K72R, K72H, K725, K72Q, K72E,K72N, K72A, K72M, R87S, Q98S, Q98A, M105F, M105I, M105V, M105L, G109A,G109S, F113W, F113S, F113N, F113Y, F113R, F113L, F113Q, R116Q, R116V,R116K, R116W, R116L, R116A, R116H, R116M, R116E, R116S, R116I, R116G,Q118N, Q118K, Q118G, Q118S, Q118F, Q118R, Q125P, Q125K, Q125A, Q125T,G133S, T134E, W140Y, G142T, G149Q, T165S, T165G, T165V, W167I, W167G,W167F, W167R, W167S, W167H, W167L, W167M, W167Y, Q169E, R171H, Q172G,Q172R, Q172N, Q172D, Q172Y, Q172M, Q172S, Q172T, Q172K, Q172H, Q172E,L173V, L173G, L173H, L173A, L173I, L173P, L173T, L173F, L173M, A174S,A174D, A174P, A174M, A174T, A174H, A174K, A174G, A174Q, A174N, A174V,A174L, G184T, A186D, A186N, A186E, A186Q, A186H, E190P, T193K, N195F,A204T, A204V, A204S, A204G, V206L, V206S, V206Y, P211D, I214G, I214H,I214S, I214T, I214L, I214E, I214W, V215T, L217T, L217Q, L219V, L219H,A225V, L235V, L235A, V238A, V238T, V238G, K242Q, S244Q, M246L, M246A,M246I, M246F, M246V, M246S, M248T, L250I, L250V, L250T, L250A, L250F,L250M, G255N, G255A, G255S, Q256A, N260G, A263G, V264I, V264T, Y267I,Y267M, Y267H, Y267L, K269Q, N270G, N270T, G273R, S280W, S280L, S280T,S280A, S280K, S280Q, W284H, T285L, T285Q, M286F, M286L, A288L, A288V,F289I, F289L, V291G, V291A, V291T, Y295N, Y295F, Q299V, S340R, S304N,R320A, R320V, H321Y, S323N, H324L, V326L, F328L, F328M, F328V, F328I,T334S, D337H, Q345D, G346T, G346D, G346P, G348S, G348P, T355L, T355F,S376H, S376T, S376V, D377H, D377S, D377A, D377Q, D379S, D379G, D379R,D379A, Y382M, Y382I, Y382L, Y382F, S383G, S383A, Q385L, K391A, K391Y,K391V, K391M, K391E, K391D, K391R, K391H, K391W, K391I, K391Q, K391L,K393Y, K393R, K393Q, K393S, Q395P, T400P, H402R, A420Q, A420S, A420K,A420L, G423H, T444Q, T444S, T444D, T444Y, T444H, T444V, T444R, T444A,A445Q, Q449T, T459N, P473R, P473A, P473G, P473T, P473K, C474V, G476K,G477A, G477Q, K484A, K484G, K484P, K484E, K484Q, and K484S of SEQ ID NO:13; or H1*, G7A, A37H, T40D, W48Y, W48F, N54S, V56T, A60V, K72R, Q98A,G109A, F113Q, R116H, R116V, R116Q, N125D, F133Q, T134E, T165G, Q169E,Q172D, Q172G, Q172N, L173V, A174S, G184T, A186D, A186N, A186E, A186Q,A186H, E190P, N195F, G196R, A204G, V206L, V206Y, A225V, L228I, K242Q,S244Q, G255A, G255S, N260G, A265G, K269Q, N270T, S280Q, W284H, A288L,A288V, F289L, Y295N, Y295F, S304N, S340R, S304N, R320A, H321Y, S323N,V326L, K391A, I405L, A421H, A422P, A428T, G448D, D476K, D476G, D476N,D476Y, G477S, G477A, G477T, and G477Q of SEQ ID NO:
 14. 15. The variantaccording to claim 1, wherein said variant has an IF of >1 when comparedto said parent polypeptide, and wherein said variant is selected from:G182*+D183*+N195F,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+R87S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+T40G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+T51K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72H+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37H+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37M+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37V+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37R+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q118N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+G142T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q125P+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q125K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381G+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246T+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V213T+K391A+G476K,H1*+A37L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q118K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q125A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377G+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377R+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214G+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381A+K391A+G476K,H1*+N54S+V56T+G109A+W167I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+W167G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346S+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214H+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214S+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214T+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420Q+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420S+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420K+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420L+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Y+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391R+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473T+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444S+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444D+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Y+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280W+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280T+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280A+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255N+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285Q+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q449T+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473K+G476K,H1*+N54S+V56T+K72S+G109A+A174S+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H1*+G109A+G182*+D183*+N195F+K391A,H1*+N54S+V56T+G109A+G133S+A174S+G182*+D183*+N195F+K391A+G476H,H1*+N54S+V56T+G109A+R116A+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37V+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+P45A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,H1*+N54S+V56T+G109A+P124A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P364A+K391A+C474V+G476K,H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,H1*+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264F+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382L+K391A+G476K,H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+Q256A+K391A+G476K,H1*+N54S+V56T+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+T165V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382F+K391A+G476K,H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q385L+K391A+G476K,H1*+N54S+V56T+R87S+G109A+R171H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,H1*+N54S+V56T+G109A+Q169E+Q172G+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+K391A+P473R+G476K,H1*+N54S+V56T+G109A+R116W+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206F+K391A+G476K,H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N260G+K391A+G476K,H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+G184T+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+A186N+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A288V+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255A+K391A+G476K,H1*+N54S+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+W48F+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+V291A+K391A+G476K,H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,H1*+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270T+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N260G+K391A+G476K,H1*+N54S+V56T+G109A+F113Q+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+A186D+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A225V+K391A+G476K,H1*+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255S+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255S+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,G182*+D183*+N195F,H1*+N54S+V56T+G109A+Q169E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+W284H+K391A+G476K,H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+S304R+K391A+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N270G+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174T+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+W140Y+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+F328L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G476K,F113Q+R116H+D183*+G182*+N195F,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A288L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K,Q169E+Q172K+A174*+D183*+G182*+N195F,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,H1*+W48F+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,F113Q+R116Q+D183*+G182*+N195F, N54S+V56T+D183*+G182*+N195F,H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,Q169E+Q172K+G182*+D183*+N195F, G182*+D183*+A186D,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,G182*+D183*+A186N,H1*+N54S+V56T+G109A+A174S+V206L+G182*+D183*+K391A+G476K,H1*+N54S+V56T+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206F+K391A+G476K,H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+A186N+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F289L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S244Q+K391A+G476K,G182*+D183*+F328L, G182*+D183*+N195F+A288V, G182*+D183*+A186N+N195F,G182*+D183*+E190P+N195F, W140Y+G182*+D183*+N195F,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A225V+K391A+G476K,G182*+D183*+A186D+N195F,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,H1*+W48Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,G182*+D183*+N195F+V238A, G182*+D183*+Y295N, Q172G+G182*+D183*,F113Q+G182*+D183*+N195F,H1*+N54S+V56T+Q98A+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,G182*+D183*+N195F+Y295F, G182*+D183*+A186E,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206Y+K391A+G476K,G182*+D183*+N195F+W284H, G182*+D183*+A186Q+N195F, K72R+G182*+D183*,D183*+G182*+N195F+V326L, D183*+G182*+A186E+N195F,Q169E+G182*+D183*+N195F, D183*+G182*+N195F+K242Q, G7A+G182*+D183*+N195F,D183*+G182*+N195F+N260G, D183*+G182*+R321A+S323N, D183*+G182*+W284H,H1*+D183*+G182*, D183*+G182*+A186H+N195F, D183*+G182*+F289V,D183*+G182*+K391A, D183*+G182*+S304R, W167F+G182*+D183*+N195F,F113Q+R116H+D183*+G182*, D183*+G182*+N270G, D183*+G182*+S244Q,H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,D183*+G182*+N195F+Y295N, W48F+D183*+G182*,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,D183*+G182*+A186Q, W140Y+D183*+G182*, D183*+G182*+K242Q,D183*+G182*+V206L, D183*+G182*+N195F+V206F, Q169E+D183*+G182*,D183*+G182*+N195F+R320A, G182*+D183*+G184T+N195F, D183*+G182*+G184T,N54S+V56T+D183*+G182*, D183*+G182*+P473R, W48Y+D183*+G182*,D183*+G182*+R323A, G7A+D183*+G182*, G109A+D183*+G182*,W167F+D183*+G182*,H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,A174S+D183*+G182*, R116Q+D183*+G182*, D183*+G182*+N195F+V291A,Q172K+D183*+G182*, N54S+D183*+G182*, D183*+G182*+N195F+S323N,D183*+G182*+N195F+M246V, W48Y+D183*+G182*+N195F,D183*+G182*+N195F+S304R, V56T+D183*+G182*, wherein numbering isaccording to SEQ ID NO: 13; and N54S+G182*+D183*+N195F,G109A+G182*+D183*+N195F, G182*+D183*+N195F+K391A,G182*+D183*+N195F+G476K, H1*+G182*+D183*+N195F, N54S+G182*+D183*+N195F,V56T+G182*+D183*+N195F, G182*+D183*+N195F+I405L,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T+D476K,A174S+G182*+D183*+N195F,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+A174S+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476G,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477S,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K,H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S304N+I405L+A421H+A422P+A428T+D476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477A,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476G+G477T,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477Q,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477A,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476K+G477Q,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476N,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476Y,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206I+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+A204G+V206L+G255A+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116H+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+T134E+A174S+G182*+D183*+N195F+G196R+V206L+G255A+I405L+A421H+A422P+A428T+N475S,H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+T40D+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+N125D+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+R116Q+G133Q+T165G+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116Q+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T+G448D,H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172 N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+F116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+A174S+M105F+G182*+D183*+N195F+V206L+L228I+R320A+S323N+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+R116Q+V120L+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,wherein numbering is according to SEQ ID NO:
 14. 16. The variantaccording to claim 1, wherein said variant is selected from the groupconsisting of:G182*+D183*+N195F+V206F+N260P+L312I+L313I+R320A+T355L+L389I+T400P,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+G50A+T51A+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G476K,H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,H1*+T40K+N54S+V56T+G109A+G149H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+Q22N+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+H28N+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N29S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+H28N+N29S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+R176K+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+R176K+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+N175G+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+Y295N+Q299T+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K269S+A274K+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235I+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+V238A+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q365S+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+H402R+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320S+H321N+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q125S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L235V+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A265G+K391A+G476K,H1*+T51Q+N54S+V56T+G109A+A174S+G182*+D183*+N195F+Y203F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+N175Q+G182*+D183*+N195F+V206L+K391A+G476K,H1*+H28N+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,H1*+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+M202V+V206L+K391A+G476K,H1*+N54S+V56T+M105F+G109A+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377H+K391A+G476K,H1*+T51G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+Y203G+V206L+K391A+G476K,H1*+T51G+N54S+V56T+G109A+G110N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q125S+A174S+N175G+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A265G+V291A+F328L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246F+A265G+V291A+F328L+Q365S+K391A+G476K,H1*+N16Y+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+G337E+D377H+K391A+G476K,H1*+19L+N54S+V56T+G109A+Q125S+V131T+A174*+G182*+D183*+V206L+Y267F+F289H+Q361E+K391A+G476K,wherein numbering is according to SEQ ID NO: 13, and wherein said IF isdetermined by use of Model A detergent.
 17. The variant according toclaim 1, wherein said variant has an IF of at least >1.5 when comparedto said parent polypeptide, and wherein said variant is selected from:H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+R87S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+T40G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+T51K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72H+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37H+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37M+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37V+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37R+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q118N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+G142T+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q125P+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q125K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381G+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246T+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V213T+K391A+G476K,H1*+A37L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q118K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q125A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377G+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377R+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214G+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381A+K391A+G476K,H1*+N54S+V56T+G109A+W167I+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+W167G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346S+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214H+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214S+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214T+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420Q+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420S+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420K+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420L+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Y+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391R+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473T+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q395P+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444S+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444D+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Y+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280W+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280T+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280A+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255N+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+T285Q+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+Q449T+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473K+G476K,H1*+N54S+V56T+K72S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+T40K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V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H1*+G109A+G182*+D183*+N195F+K391A,H1*+N54S+V56T+G109A+G133S+A174S+G182*+D183*+N195F+K391A+G476H,H1*+N54S+V56T+G109A+R116A+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37V+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+P45A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,H1*+N54S+V56T+G109A+P124A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P364A+K391A+C474V+G476K,H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,H1*+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264F+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382L+K391A+G476K,H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+Q256A+K391A+G476K,H1*+N54S+V56T+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+T165V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382F+K391A+G476K,H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q385L+K391A+G476K,H1*+N54S+V56T+R87S+G109A+R171H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,G109A+G182*+D183*+N195F, G182*+D183*+N195F+K391A,H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,H1*+N54S+V56T+G109A+Q169E+Q172G+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+K391A+P473R+G476K,H1*+N54S+V56T+G109A+R116W+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206F+K391A+G476K,H1*+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N260G+K391A+G476K,H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+G184T+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295N+K391A+G476K,H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+A186N+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A288V+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255A+K391A+G476K,H1*+N54S+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+W48F+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+V291A+K391A+G476K,H1*+N54S+V56T+G109A+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+R320A+S323N+K391A+G476K,H1*+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270T+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N260G+K391A+G476K,H1*+N54S+V56T+G109A+F113Q+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+A186D+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+A225V+K391A+G476K,H1*+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+G255S+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255S+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,G182*+D183*+N195F,H1*+N54S+V56T+G109A+Q169E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+W284H+K391A+G476K,H1*+N54S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+S304R+K391A+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246V+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+N270G+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174T+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+W140Y+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+F328L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G476K,F113Q+R116H+D183*+G182*+N195F,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+A288L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+N270G+K391A+G476K,Q169E+Q172K+A174*+D183*+G182*+N195F,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K269Q+K391A+G476K,H1*+W48F+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,F113Q+R116Q+D183*+G182*+N195F, N54S+V56T+D183*+G182*+N195F,H1*+N54S+V56T+G109A+A174T+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,Q169E+Q172K+G182*+D183*+N195F, G182*+D183*+A186D,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V238A+K391A+G476K,G182*+D183*+A186N,H1*+N54S+V56T+G109A+A174S+V206L+G182*+D183*+K391A+G476K,H1*+N54S+V56T+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206F+K391A+G476K,H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+A186N+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+F289L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y295F+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V291A+K391A+G476K,G182*+D183*+A186N+N195F, G182*+D183*+A186D+N195F,G182*+D183*+N195F+W284H, D183*+G182*+N195F+V326L, wherein numbering isaccording to SEQ ID NO: 13, andH1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476G+G477T,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477Q,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+G477A,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476N,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+I405L+A421H+A422P+A428T+D476Y,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206I+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+T134E+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+T40D+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+N125D+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116H+Q172G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172 N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+F116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+R116Q+V120L+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,wherein numbering is according to SEQ ID NO: 14, and wherein said IF isdetermined by use of Model A detergent.
 18. The variant according toclaim 1, wherein said variant has an IF of at least >2.0 when comparedto said parent polypeptide, and wherein said variant is selected from:H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+R87S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+T40G+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+T51K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72H+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37H+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37M+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37V+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37Y+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37R+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113W+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+F113N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116K+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q125P+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381G+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+M246T+K391A+G476K,H1*+A37L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q125A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377S+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+D377A+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S381A+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346P+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214H+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214S+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420Q+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420S+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420K+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+A420L+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Y+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+P473G+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444D+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444Y+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280W+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+S280L+K391A+G476K,H1*+N54S+V56T+K72S+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+T40K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K,H1*+G50A+N54S+V56T+G109A++Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K+K484S,H1*K+G50A+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204T+V206L+K391A+G476K,H1*+N54S+V56T+G109A+W140Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,H1*+N54S+V56T+G109AG255A++A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+G50A+N54S+V56T+G109A+F113L+R116L+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+W167F+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320V+K391A+G476Y,H1*+N54S+V56T+G109A+R116M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q172Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I214L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217V+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+L217H+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P211D+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+K391Q+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444H+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444V+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+T444R+G476K,H1*+G50A+N54S+V56T+G109A+L173V+A174S+G182*+D183*+N195F+A204V+V206L+K391A+G476K,H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+R320A+K391A+G476K,H1*+N54S+V56T+G109A+Q172D+A174S+G182*+D183*+N195F+V206L+G346T+K391A+G476K+G477A,H1*+N54S+V56T+G109A+Q118S+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V2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H1*+N54S+V56T+A60V+G109A+R116H+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37V+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37H+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+A60V+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,H1*+N54S+V56T+A60V+G109A+R116Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116A+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,H1*+N54S+V56T+G109A+G182*+D183*+N195F+K391A+G476K,H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L,N54S+V56T+G109A+G182*+D183*+N195F,N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+G476K,H1*+N54S+V56T+A174S+G182*+D183*+N195F+V206L+G273R+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L,N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,H1*+N54S+V56T+G109A+F113Q+Q172M+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+T134E+A174S+G182*+D183*+N195F+V206L+G255A+K391A+P473R+G476K,H1*+N54S+V56T+K72R+G109A+R116Q+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,H1*+A37V+N54S+V56T+G109A+R116A+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,H1*+V56A+G109A+A174S+G182*+D183*+N195F+V206L+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116H+A174S+G182*+D183*+G184T+N195F+V206L+K391A+T444Q+G476K,H1*+N54S+V56T+G109S+F113Q+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+G476K,H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,H1*+N54S+V56T+G109A+F113Q+W167F+Q172N+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+R116A+A174S+G182*+D183*+N195F+V206L+K391A+T444Q+P473R+G476K,H1*+N54S+V56T+G109A+R116H+Q172R+A174S+G182*+D183*+N195F+A204G+V206L+K391A+P473R+G476K,H1*+A37V+N54S+V56T+G109A+R116Q+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37H+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+M246F+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+K391A+G476K,H1*+N54S+V56T+G109A+G133S+A174S+G182*+D183*+N195F+K391A+G476H,H1*+N54S+V56T+G109A+R116A+Q172N+L173V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+A37V+N54S+V56T+G109A+R116H+T165G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+P45A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+C474V+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+P364A+K391A+C474V+G476K,H1*+N54S+V56T+G109A+Q118R+T134E+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,H1*+G50A+T51A+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+V264F+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382L+K391A+G476K,H1*+G7K+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+G255A+Q256A+K391A+G476K,H1*+N54S+V56T+G109A+W167Y+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+W167H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+T165V+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174N+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174Q+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N16H+V17L+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Y382F+K391A+G476K,H1*+Q32S+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+Q385L+K391A+G476K,H1*+N54S+V56T+R87S+G109A+R171H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116H+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+P473R+G476K,H1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andH1*+N54S+V56T+G109A+Q169E+Q172K+A174S+G182*+D183*+N195F+V206L+K391A+G476K;wherein numbering is according to SEQ ID NO: 13, andH1*+T40D+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+N125D+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116H+Q172N+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+T134E+W167F+Q172N+A174S+G182*+D183*+N195F+V206L+G255A+A265G+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+L173V+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+F113Q+T134E+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+G255A+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+A204G+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+K72R+G109A+R116Q+V120L+A174S+G182*+D183*+G184T+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116H+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+I405L+A421H+A422P+A428T,H1*+A37H+N54S+V56T+A60V+G109A+R116Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+I405L+A421H+A422P+A428T,wherein numbering is according to SEQ ID NO: 14, and wherein said IF isdetermined by use of Model A detergent.
 19. The variant according toclaim 1, wherein said variant is selected from a group consisting of:H1*+N54S+V56T+G109A+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+Q169E+Q172K+A174*+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116H+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+G109A+R116Q+W167F+A174S+G182*+D183*+G184T+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+F113Q+R116Q+W167F+Q172G+A174S+G182*+D183*+G184T+N195F+V206L+K391A+P473R+G476K,H1*+N54S+V56T+G109A+F113Q+R116Q+Q172N+A174S+G182*+D183*+N195F+V206L+A265G+K391A+P473R+G476K,H1*+N54S+V56T+K72R+G109A+G133Q+W167F+Q172R+A174S+G182*+D183*+N195F+V206L+K391A+G476K,H1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+G476K,andH1*+N54S+V56T+K72R+G109A+R116H+T134E+W167F+Q172G+L173V+A174S+G182*+D183*+N195F+V206L+G255A+K391A+Q395P+T444Q+P473R+G476K,wherein numbering is according to SEQ ID NO:
 13. 20. A compositioncomprising a variant according to claim
 1. 21. The composition accordingto claim 20, wherein said composition further comprises at least onefurther active component.
 22. The composition according to claim 20,wherein said further active component is an enzyme selected from thegroup consisting of a protease, a lipase, a cellulose, a pectate lyaseand a mannanase.
 23. The composition according to claim 20, which is aliquid laundry or liquid dish wash composition, such as an AutomaticDish Wash (ADW) liquid detergent composition, or a powder laundry, suchas a soap bar, or powder dish wash composition, such as an ADW unit dosedetergent composition and such as a Hand Dish Wash (HDW) detergentcomposition.
 24. The composition according to claim 20, wherein saidcomposition further comprises a surfactant, builder, bleach, polymer, orwherein said composition is phosphate-free.
 25. An polynucleotideencoding the variant according to claim
 1. 26. A nucleic acid constructcomprising the polynucleotide according to claim
 25. 27. An expressionvector comprising the polynucleotide according to claim
 25. 28. A hostcell comprising the polynucleotide according to claim
 25. 29. A methodof producing an alpha-amylase variant, comprising: a. cultivating thehost cell of claim 28 under conditions suitable for expression of saidvariant; and b. recovering said variant.
 30. A method of improving washperformance of a parent polypeptide having the amino acid sequence ofSEQ ID NO: 13 or 14, or having at least 80% sequence identity thereto,said method comprising the steps of: a) a substitution and/or deletionof two, three or four positions in the parent alpha-amylase saidpositions corresponding to positions 181, G182, D183, and G184 of themature polypeptide of SEQ ID NO: 4; and b) an alteration at one or morepositions corresponding to positions H1, T5, G7, Q11, N16, V17, Q32,A37, T40, P45, W48, G50, T51, N54, V56, K72, R87, Q98, M105, G109, F113,R116, Q118, Q125, G133, T134, W140, G142, G149, T165, W167, Q169, R171,Q172, L173, A174, G184, A186, E190, T193, N195, A204, V206, P211, I214,V215, L217, L219, A225, L235, V238, K242, S244, M246, M248, L250, G255,Q256, N260, A263, V264, Y267, K269, N270, G273, S280, W284, T285, M286,F289, V291, N295, Q299, R320, H321, S323, H324, V326, F328, T334, D337,Q345, G346, G348, T355, S376, D377, D379, Y382, S383, Q385, K391, K393,Q395, A420, G423, T444, A445, Q449, T459, P473, C474, G476, G477, andK484 of SEQ ID NO: 13; or H1, A37, T40, N54, V56, A60, K72, G109, F113,R116, N125, F133, T134, T165, Q169, Q172, L173, A174, G184, A186, E190,N195, G196, A204, V206, A225, L228, K242, S244, G255, N260, A265, K269,S280, W284, N295, S304, R320, H321, S323, V326, K391, I405, A421, A422,A428, G448, D476, and G477 of SEQ ID NO: 14, wherein the variant has atleast 80% but less than 100% sequence identity with the polypeptide ofSEQ ID NO: 4 or 7, and wherein said variant has alpha-amylase activityand improved wash performance compared to said parent polypeptide. 31.The method according to claim 30, wherein said variant has at least 50%,at least 60%, at least 70%, at least 80%, at least 90%, at least 100% ofthe activity of said parent polypeptide having the amino acid sequenceof SEQ ID NO:
 7. 32. The method according to claim 30, wherein saidactivity is determined according to a Phadebas assay.
 33. (canceled)